Rab29 activation of the Parkinson's disease‐associated LRRK2 kinase

Name: Work Video:
Duration: 3 min 30 s
Elena Purlyte; Herschel S. Dhekne; Adil R. Sarhan; Rachel C. Gomez; Paweł Lis; Melanie Wightman; Terina N. Martinez; Francesca Tonelli; Suzanne R. Pfeffer; Dario R. Alessi
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[184, 455, 624], 'Francesca': [193, 197, 464, 468, 576], 'Tonelli': [194, 198, 465, 469, 577], 'Corresponding': [195, 227, 256, 466, 498, 527], 'Author': [196, 228, 257, 467, 499, 528, 557], '[email': [199, 232, 261, 470, 503, 532, 640, 650, 659], 'protected]': [200, 233, 262, 471, 504, 533, 641, 651, 660], 'orcid.org/0000-0002-4600-6630': [201, 472], 'Suzanne': [224, 229, 495, 500, 579], 'Pfeffer': [226, 231, 497, 502, 581], 'orcid.org/0000-0002-6462-984X': [234, 505], 'Dario': [253, 258, 524, 529, 584], 'Alessi': [255, 260, 526, 531, 586], 'orcid.org/0000-0002-2140-9185': [263, 534], 'Information': [558], 'Purlyte1,‡,': [560], 'Dhekne2,‡,': [563], 'Sarhan1,': [566], 'Gomez2,': [568], 'Lis1,': [570], 'Wightman1,': [572], 'Martinez3,': [575], '*,1,‡,': [578], '*,2': [582], '*,1': [587], '1MRC': [588], '2Department': [603], '3The': [614], '‡These': [626], 'authors': [627], 'contributed': [628], 'equally': [629], 'to': [630, 705, 708, 766, 790, 924, 946, 953, 994, 1033, 1240, 1261, 1311, 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[688], 'a': [689, 724, 754, 853, 872, 892, 1042, 1064, 1073, 1080, 1088, 1096, 1175, 1385, 1460, 1605, 1647, 1725, 1746, 1767, 1826, 1877, 1950, 1994, 2002, 2037, 2064, 2162, 2182, 2246, 2348, 2771, 2909, 3001, 3337, 3431, 3493, 3537, 3874, 3994, 4262, 4320], 'summary': [690], 'editorial': [693, 697], 'decision': [694, 698], 'including': [696, 730, 1154, 1663, 1901, 2730, 2781], 'letters,': [699], 'reviewer': [700], 'comments': [701], 'responses': [704], 'feedback.': [706], 'ToolsAdd': [707], 'favoritesDownload': [709], 'CitationsTrack': [710], 'CitationsPermissions': [711], 'ShareFacebookTwitterLinked': [712], 'InMendeleyWechatReddit': [713], 'Figures': [714], '&': [715, 1228, 1442], 'Info': [716], 'Abstract': [717], 'disease': [719, 996, 1035, 1127, 1415], 'predisposing': [720], 'phosphorylates': [723, 1927], 'group': [725], 'Rab': [727, 1074, 1151, 1179, 1216, 1241, 1249, 1309, 1661, 2286, 2310, 2426, 2728, 2779, 2806, 2858, 3328, 4048, 4337], 'GTPase': [728, 887, 1066, 1075, 1152, 1280, 4049], 'proteins': [729, 1180, 1217, 1237, 1662, 2287, 2729, 2780, 2807, 3174, 3474, 3529, 3546, 3721, 4123, 4126], 'Rab29,': [731, 742, 1186, 1453, 2659, 3452, 3472], 'within': [732, 744, 804, 984, 1108, 1219, 1278, 1408, 1464, 1474, 1491, 1527, 4310], 'effector-binding': [734, 1468], 'switch': [735, 1222], 'II': [736, 1223, 1467], 'motif.': [737], 'Previous': [738], 'indicated': [740, 2416, 2424, 2500, 2529, 2565, 2590, 2856, 2872, 3327, 3331, 3373], 'that': [741, 762, 782, 809, 837, 839, 869, 901, 903, 1070, 1118, 1190, 1245, 1380, 1434, 1504, 1533, 1594, 1619, 1630, 1642, 1657, 1704, 1744, 1946, 1978, 1983, 2016, 2029, 2061, 2288, 2330, 2357, 2422, 2556, 2581, 2646, 2661, 2695, 2707, 2726, 2755, 3251, 3378, 3778, 3799, 4018, 4304], 'located': [743, 1277, 1561], 'PARK16': [746, 1410, 1476, 1493, 1506], 'locus': [747, 1411, 1477, 1494, 1507], 'mutated': [748, 1030, 2638, 2687], 'in': [749, 753, 826, 1006, 1017, 1293, 1320, 1377, 1589, 1604, 1646, 1748, 1784, 1815, 1868, 1869, 2011, 2067, 2106, 2214, 2393, 2419, 2432, 2546, 2552, 2573, 2578, 2607, 2613, 3090, 3096, 3136, 3191, 3202, 3269, 3295, 3304, 3311, 3329, 3469, 3503, 3539, 3693, 3742, 3880, 3895, 4026, 4124, 4164, 4179, 4290, 4319], 'patients,': [751, 1022], 'operates': [752], 'common': [755, 1104, 1525, 1648], 'pathway': [756, 1607, 1649], 'with': [757, 820, 844, 1079, 1570, 1986, 2019, 2099, 2190, 2264, 2274, 2382, 2414, 2430, 2445, 2457, 2469, 2498, 2508, 2527, 2587, 2765, 2841, 2849, 2870, 2890, 2933, 2938, 3025, 3030, 3118, 3237, 3248, 3267, 3325, 3417, 3450, 3471, 3511, 3534, 3556, 3565, 3576, 3596, 3624, 3648, 3665, 3675, 3687, 3785, 3802, 3811, 3829, 3842, 3859, 3889, 3901, 4046, 4076, 4083, 4129], 'LRRK2.': [758, 799, 958, 2716], 'Here,': [759], 'we': [760, 1944, 2096, 2637, 2686, 3160, 4260], 'show': [761, 836, 3613, 3639, 3654, 3798], 'recruits': [764, 922, 936, 1706], 'trans-Golgi': [768, 926, 3740, 3876], 'network': [769, 927, 3741, 3877], 'greatly': [771, 929], 'stimulates': [772, 930], 'its': [773, 878, 931, 1263, 2022, 2203, 2669, 2712, 3438, 3803], 'activity.': [775, 933, 2366], 'Pathogenic': [776, 1275, 3552], 'R1441G/C': [778, 942, 1369, 2177], 'Y1699C': [780, 944, 1371, 2179], 'mutants': [781, 941, 1373, 1982, 2103, 2180, 2198, 2233, 2253, 2300, 2591, 3554], 'promote': [783, 947, 1332], 'GTP': [784, 848, 949, 965, 1333, 1382, 1985], 'binding': [785, 906, 966, 1239, 1258, 1334, 1383, 1672, 1751], 'are': [786, 810, 1015, 1163, 1191, 1374, 1435, 1495, 1773, 1989, 2284, 2289, 2735, 3210, 3246, 3255, 3280, 4216, 4221], 'readily': [788], 'recruited': [789], 'Golgi': [792, 814, 1710, 2070, 3106, 3408, 3495, 3560, 3644, 3717, 3763, 3782, 3823], 'activated': [794, 1990, 2241, 2651, 2785, 3968, 4297], 'than': [797, 1316, 1998, 2166, 2186, 2249, 2801, 3230, 3996, 4287], 'wild-type': [798, 1999, 2100, 2167, 2187, 2237, 2501, 2533, 2588, 2658, 2745, 2757, 2843], 'We': [800, 835, 1976, 2327, 2644, 2721, 2753], 'identify': [801], 'conserved': [802], 'residues': [803, 1086, 1729, 1863, 4239, 4272, 4331], 'ankyrin': [807, 955, 1056, 1733, 2024, 4277], 'domain': [808, 956, 1052, 1057, 1067, 1082, 1092, 1099, 1111, 1339, 1734, 4238, 4330], 'required': [811, 1247, 1881, 2632, 2667, 4256], 'Rab29-mediated': [813], 'recruitment': [815], 'activation.': [818], 'Consistent': [819], 'these': [821, 1215, 1545, 1643, 1802, 1841, 1886, 1919, 2196, 2438, 2639, 3216, 3796], 'findings,': [822], 'knockout': [823, 4032], 'A549': [827], 'cells': [828, 1378, 2379, 2390, 2434, 2495, 2520, 2838, 2863, 3193, 3282, 3470, 3510, 3562, 3581, 3664, 3690, 3851, 3872, 3892, 3947, 4035, 4073, 4088], 'reduces': [829], 'endogenous': [830, 2124, 3451, 3460], 'LRRK2-mediated': [831], 'phosphorylation': [832, 851, 859, 968, 973, 1203, 1232, 1255, 1307, 1462, 1839, 1969, 2035, 2043, 2080, 2122, 2146, 2262, 2320, 2323, 2338, 2361, 2622, 2662, 2681, 2689, 2709, 2743, 2799, 2817], 'Rab10.': [834, 1975], 'mutations': [838, 960, 983, 1276, 1331, 1490, 2007, 2028], 'prevent': [840, 2034], 'from': [842, 1933, 3336, 3363, 3886, 4030, 4188], 'interacting': [843], 'either': [845, 962, 2509, 2850, 3289], 'or': [847, 964, 1637, 2306, 2384, 2397, 2471, 2475, 2513, 2846, 2854, 3292, 3567, 3569, 3604, 3625, 3843, 4053, 4055], 'strikingly': [849], 'inhibit': [850, 908, 967], 'cluster': [854, 1726, 2038], 'highly': [856, 2040, 2736], 'studied': [857, 2041], 'biomarker': [858, 883, 972, 1810, 1842, 1862, 2042, 2082], 'sites': [860, 974, 1764, 1887, 1931, 2044, 2640, 2690], '(Ser910,': [861, 1739, 2045], 'Ser935,': [862, 1740, 1805, 2046], 'Ser955': [863, 1741, 2047], 'Ser973).': [865], 'Our': [866, 2013, 2058], 'data': [867, 1854, 3797, 4008, 4220], 'reveal': [868, 3176], 'is': [871, 889, 1041, 1077, 1246, 1379, 1402, 1425, 1471, 1486, 1568, 1721, 1831, 1880, 2280, 2465, 2532, 2665, 3112, 3199, 3404, 3489, 4023, 4282], 'master': [873, 893], 'regulator': [874, 894, 1953], 'LRRK2,': [876, 2000, 2188, 2636, 2685, 2758, 2906], 'controlling': [877, 1608], 'activation,': [879, 4259], 'localization,': [880], 'potentially': [882, 2078], 'phosphorylation.': [884], 'Synopsis': [885], 'found': [890, 1524, 2329, 2645, 2754], 'as': [891, 1161, 1396, 1540, 1771, 1949, 1966, 1968, 1974, 2075, 2077, 2119, 2121, 2334, 2336, 2452, 2657, 2881, 3497, 3632, 3846, 3878, 4051, 4114], 'kinase,': [899], 'suggesting': [900, 1117, 2001], 'inhibitors': [902, 1120, 1789, 1820], 'block': [904], 'might': [907, 1121], 'activity': [910, 1292, 1837, 1936, 2010, 2074, 2151, 2213], 'offer': [912, 1122], 'therapeutic': [913, 1123], 'potential': [914, 1192], 'treatment': [917, 2468, 3508, 3760], 'disease.': [920, 1499], 'preferentially': [935], 'activates': [938, 2086, 2491, 2719, 2833, 3103], 'pathogenic': [939, 1105, 1980, 2102, 2197, 2232, 2505, 2567, 2583, 3544, 3719], 'known': [945, 1160, 1895], 'binding.': [950], 'binds': [952], 'preventing': [961], 'well-studied': [970], '(S910,': [975], 'S935,': [976], 'S955,': [977], 'S973).': [978], 'Introduction': [979], 'Autosomal': [980], 'dominant': [981], 'missense': [982], 'leucine-rich': [986, 1060, 1736], 'repeat': [987, 1051, 1737], 'protein': [988, 1045, 1090, 1250, 3128, 3154, 3198, 3220, 3239, 3419, 4101], '2': [990, 3184, 3317], '(LRRK2)': [991], 'gene': [992, 1578], 'predispose': [993], '(Paisan-Ruiz': [997], 'et': [998, 1002, 1037, 1129, 1133, 1137, 1141, 1145, 1168, 1198, 1271, 1296, 1300, 1323, 1327, 1341, 1345, 1349, 1353, 1357, 1361, 1417, 1421, 1447, 1513, 1552, 1556, 1584, 1612, 1651, 1680, 1684, 1688, 1692, 1696, 1713, 1717, 1756, 1760, 1791, 1795, 1822, 1889, 1904, 1910, 1938, 2051, 2055, 2116, 2294, 3260, 3411, 3727, 3731, 4324], 'al,': [999, 1003, 1038, 1130, 1134, 1138, 1142, 1146, 1169, 1199, 1272, 1297, 1301, 1324, 1328, 1342, 1346, 1350, 1354, 1358, 1362, 1418, 1422, 1448, 1514, 1553, 1557, 1585, 1613, 1652, 1681, 1685, 1689, 1693, 1697, 1714, 1718, 1757, 1761, 1792, 1796, 1823, 1890, 1905, 1911, 1939, 2052, 2056, 2117, 2295, 3261, 3412, 3728, 3732, 4325], '2004;': [1000], 'Zimprich': [1001], '2004).': [1004], 'Mutations': [1005], 'account': [1008, 1851, 2315], '~5%': [1010], 'familial': [1012], "Parkinson's,": [1013], 'observed': [1016, 1867, 2324, 2694], '~1%': [1018], 'sporadic': [1020], 'making': [1023], 'one': [1025, 1403], 'most': [1028, 1103, 1426], 'commonly': [1029], 'genes': [1031, 1406, 1532, 1644], 'linked': [1032, 1412, 1496], '(Simon-Sanchez': [1036, 1416], '2009).': [1039], 'large,': [1043], 'multi-domain': [1044], 'consisting': [1047], 'an': [1049, 1055, 1312, 1395, 1626, 2446, 2458, 2479, 2677, 3162, 3479, 3812, 4247], 'armadillo': [1050, 4275], '(residues': [1053, 1058, 1062, 1068, 1093, 1100], '150–510),': [1054], '690–860),': [1059], 'repeats': [1061], '984–1278),': [1063], 'ROC-type': [1065], '1335–1510)': [1069], 'closely': [1071, 1427], 'resembles': [1072], 'associated': [1078, 1569, 3659], 'COR': [1081, 1283], '(C-terminal': [1083], 'Roc,': [1085], '1511–1878),': [1087], 'serine/threonine': [1089], '1879–2138),': [1094], 'WD40': [1097], 'repeat-containing': [1098], '2142–2496).': [1101], 'mutation': [1106, 1319, 2351, 2472, 2560, 2597], 'lies': [1107, 1218, 4309], 'catalytic': [1110], '(G2019S)': [1112], 'increases': [1114, 4064], 'activity,': [1116, 1778, 1959, 2095, 2206], 'benefit': [1124], '(Greggio': [1128], '2006;': [1131, 1135, 1139], 'Ozelius': [1132], 'Smith': [1136], 'Jaleel': [1140], '2007;': [1143, 1298, 1343, 1347, 1351], 'Hatcher': [1144], '2017).': [1147, 1200, 1274, 1824], 'Members': [1148], 'family,': [1153], 'Rab8A,': [1155], 'Rab10,': [1156, 1184], '(also': [1159], 'RAB7L1),': [1162], 'substrates': [1164, 1194, 1972, 3258], '(Steger': [1167, 1197, 1270, 2293, 3259], '2016).': [1170, 1329, 1614, 1653, 3262], 'Recent': [1171], 'has': [1173, 1502, 1580, 1700, 1806, 1864, 3722], 'defined': [1174], 'subset': [1176], '14': [1178, 2285], '(Rab3A/B/C/D,': [1181], 'Rab5A/B/C,': [1182], 'Rab8A/B,': [1183], 'Rab12,': [1185, 2768], 'Rab35,': [1187], 'Rab43)': [1189], 'direct': [1193], 'site': [1204, 1463], '(Thr72': [1205], 'Rab8A': [1207, 1234, 1260, 2811, 2963, 3055, 4052], 'Thr73': [1209, 2461], 'Rab10)': [1211], 'all': [1213, 2896], 'effector-binding,': [1221], 'motif': [1224], '(Pfeffer,': [1225], '2001;': [1226], 'Cherfils': [1227], 'Zeghouf,': [1229], '2013).': [1230], 'Rab10': [1236, 2125, 2145, 2261, 2322, 2337, 2476, 2971, 3063, 3219, 3252, 3268, 3805], 'blocks': [1238], 'GDP-dissociation': [1242], 'inhibitor': [1243, 2403, 3516], '(GDI)': [1244], 'membrane': [1251, 3382, 3938, 3956, 4027, 4065, 4096, 4100, 4165], 'delivery': [1252], 'recycling;': [1254], 'also': [1256, 1617, 1701, 1914, 2173, 2314, 2328, 2795, 2814, 3000, 3211, 3217, 3429, 3809, 3991, 4024, 4317], 'inhibits': [1257], 'Rabin-8,': [1262], 'cognate': [1264], 'guanine': [1265], 'nucleotide': [1266], 'exchange': [1267], 'factor': [1268, 1879], '(GEF)': [1269], '2016,': [1273], '(R1441G/C)': [1281], '(Y1699C)': [1284], 'domains': [1285, 1673], 'do': [1286, 1457], 'not': [1287, 1458, 1675, 1865, 1894, 2666, 3913, 4199, 4217, 4296], 'directly': [1288], 'stimulate': [1289, 1883, 2008], 'vitro': [1294, 1870], '(Jaleel': [1295], 'Nichols': [1299], '2010);': [1302], 'nevertheless,': [1303], 'they': [1304, 1772], 'markedly': [1305, 2760, 2796], 'enhance': [1306], 'isoforms': [1310, 2427], 'even': [1313], 'greater': [1314, 1996, 2164, 2184, 3995], 'extent': [1315, 1997, 2165, 2185, 2248, 2266, 2656, 3780], 'G2019S': [1318, 2208, 3428, 3466, 3524], 'vivo': [1321, 1816], '(Ito': [1322], '2016;': [1325], 'Steger': [1326], 'These': [1330, 1763, 3244], 'Roc': [1338], '(Guo': [1340], 'Lewis': [1344], 'Li': [1348], 'Daniels': [1352], '2011;': [1355, 1359], 'Webber': [1356], 'Liao': [1360], '2014).': [1363, 1449, 1515, 1719, 4326], 'One': [1364], 'explanation': [1365], 'why': [1367], 'active': [1376, 3941, 4161], 'enhanced': [1381, 2140, 2223, 2251], 'induces': [1384], 'conformational': [1386], 'change,': [1387], 'rendering': [1388], 'susceptible': [1391], 'yet': [1397, 1676], 'unknown,': [1398], 'upstream': [1399, 1600, 1952], 'activator.': [1400], 'five': [1405], 'contained': [1407], '2009;': [1419], 'Tucci': [1420], '2010).': [1423, 1891], 'It': [1424, 1615, 1699], 'related': [1428, 2737], 'Rab32': [1430, 1454, 2731, 2782, 2983, 3075], 'Rab38': [1432, 1456, 2733, 2784, 2813, 2987, 3079], 'GTPases': [1433], 'needed': [1436], 'lysosome-related': [1438], 'organelle': [1439], 'biogenesis': [1440], '(Bultema': [1441], 'Di': [1443], 'Pietro,': [1444], '2013;': [1445, 1554, 1686, 1715, 3729], 'Wang': [1446], 'In': [1450, 1921, 1941, 2256, 2676, 3225, 4246], 'contrast': [1451], 'possess': [1459], 'their': [1465, 3963], 'Switch': [1466], 'motifs.': [1469], 'There': [1470], 'significant': [1472, 2911, 3003, 3256, 3476, 3914, 4200], 'variability': [1473], 'association': [1480, 4043, 4066], 'patterns': [1481], 'across': [1482], 'populations,': [1483], 'it': [1485, 1830, 3415, 4293], 'currently': [1487, 1832], 'unclear': [1488, 1833], 'how': [1489, 1834], 'Transcriptome': [1500], 'analysis': [1501, 3737], 'suggested': [1503, 1656, 4318], 'enhances': [1508], 'expression': [1509, 2279, 3821, 4171], '(Beilina': [1512, 4323], 'Other': [1516, 1892], 'genetic': [1517, 1542], 'studies': [1518, 1871, 2014], 'patient': [1521], 'cohorts': [1522], 'have': [1523, 1655, 1674, 1765, 1913, 2302, 2740], 'variants': [1526, 1543, 1579, 2507], 'function': [1534], 'coordinately': [1535], 'increase': [1537], 'risk,': [1539], 'human': [1541, 2503], 'at': [1544, 1724, 2625, 3615, 4117, 4284], 'loci': [1546], 'impact': [1547], 'risk': [1549], 'non-additively': [1550], '(MacLeod': [1551, 1712, 3726], 'Pihlstrom': [1555], '2015).': [1558, 1586, 1698], 'A': [1559, 3442], 'haplotype': [1560], 'near': [1562, 3274], '5′': [1564], 'region': [1565, 1738, 3205, 3506, 4253, 4308], 'RAB29': [1567, 1596], 'epistasis': [1573], 'between': [1574, 1731, 2318, 2913, 3005, 3907, 4210], 'been': [1581, 1677, 1702, 1866, 1915, 3723], 'demonstrated': [1582], '(Pihlstrom': [1583], 'Genetic': [1587], 'investigations': [1588], 'Caenorhabditis': [1590], 'elegans': [1591], 'neurons': [1592], 'revealed': [1593], '(GLO-1)': [1597], 'orthologue': [1598], 'acts': [1599], '(LRK-1)': [1603], 'signaling': [1606], 'axon': [1609], 'termination': [1610], '(Kuwahara': [1611, 1650], 'was': [1616, 1631, 2172, 2221, 2344, 2359, 2561, 2585, 2631, 2908, 2999, 3334, 3467, 4294, 4316], 'reported': [1618, 1703, 1916, 3725], 'double-knockout': [1623], 'mice': [1624], 'exhibit': [1625], 'enlarged': [1627, 3308], 'kidney': [1628], 'phenotype': [1629], 'non-additive,': [1632], 'relative': [1633, 3787], 'single': [1635], 'knockout,': [1639], 'further': [1640, 2222], 'implying': [1641], 'act': [1645], 'Others': [1654], 'various': [1660], 'interact,': [1665], 'largely': [1666], 'based': [1667], 'on': [1668, 2741, 3105, 3437, 3547, 3937, 4003, 4152], 'co-immunoprecipitation': [1669], 'analysis,': [1670], 'but': [1671, 2764, 2810, 3206, 3453], 'pinpointed': [1678], '(Dodson': [1679], '2012;': [1682], 'MacLeod': [1683], 'Beilina': [1687, 1716, 3730], '2014;': [1690, 1694], 'Waschbusch': [1691], 'Zhang': [1695], 'apparatus': [1711], 'constitutively': [1722], 'phosphorylated': [1723, 2174, 2290], 'Ser': [1728], 'lying': [1730], 'Ser973)': [1743, 2049], 'plays': [1745, 2063], 'role': [1747, 2066], 'regulating': [1749, 2068], '14-3-3': [1750], 'cytosolic': [1753, 3152, 3173, 4111], 'localization': [1754, 2071, 2305, 3131, 3178, 3187, 3764], '(Nichols': [1755], '2010;': [1758, 1793, 2053], 'Doggett': [1759, 1794, 2054], '2011).': [1762, 1797, 2057], 'received': [1766], 'lot': [1768, 1827], 'attention': [1770], 'controlled': [1774], 'therefore': [1780], 'become': [1781, 1807], 'rapidly': [1782], 'dephosphorylated': [1783], 'response': [1785], 'diverse': [1787, 2309], '(Dzamko': [1790, 1888, 1937, 2050], 'Monitoring': [1798], 'dephosphorylation': [1800], 'residues,': [1803], 'especially': [1804], 'principal': [1809], 'strategy': [1811], 'assess': [1813], 'efficacy': [1817], '(Hatcher': [1821], 'Despite': [1825], 'research,': [1829], 'influences': [1838, 2092], 'sites.': [1843, 1920, 2083], 'Autophosphorylation': [1844], 'would': [1845, 3932], 'be': [1846, 1897, 3933], 'simplest': [1848], 'model': [1849, 3538], 'obtained': [1855, 2545, 2572, 2606, 3089, 4010, 4029], 'date.': [1857], 'However,': [1858, 3463], 'autophosphorylation': [1859, 1884, 1963, 2112], 'undertaken': [1872], 'thus': [1873], 'far,': [1874], 'perhaps': [1875], 'indicating': [1876, 2660, 4303], 'missing': [1878], 'kinases': [1893], 'regulated': [1898], 'CK1': [1902], '(Chia': [1903], '2014)': [1906, 1912, 3413], 'PKA': [1908], '(Muda': [1909], 'phosphorylate': [1918, 2437], 'macrophages,': [1922], 'IkappaB': [1924], 'family': [1926], 'Ser910': [1928], 'Ser935': [1930], 'independently': [1932], '2012).': [1940], 'study,': [1943], 'demonstrate': [1945], 'functions': [1948], 'critical': [1951], 'stimulating': [1957, 2363], 'inferred': [1960], 'assessing': [1962], 'Ser1292': [1965, 2114, 2143, 2319, 2333, 2742, 2762, 2798, 2816], 'well': [1967, 2076, 2120, 2335], 'such': [1973, 2006, 4050], 'find': [1977], 'bind': [1984], 'higher': [1987, 2192, 2204], 'affinity': [1988], 'much': [1995, 2163, 2183, 3500], 'mechanism': [2003], 'which': [2005, 2220, 2312, 2769, 3540, 4315], 'vivo.': [2012], 'suggest': [2015, 2060], 'interacts': [2018], 'via': [2021], 'N-terminal': [2023, 4313], 'domain,': [2025], 'and,': [2026], 'strikingly,': [2027], 'disrupt': [2030], 'regulation': [2031], 'findings': [2059, 3245], 'major': [2065], 'triggering': [2079], 'Results': [2084, 3087], 'To': [2088, 2619, 3139, 3944], 'explore': [2089], 'whether': [2090, 2621], 'co-expressed': [2097, 2429, 3468], 'HEK293': [2107, 2378, 2433, 2494, 2837, 4291], 'cells,': [2108, 4292], 'assessed': [2110], '(Sheng': [2115], '2012)': [2118], '(Thr73)': [2126], '(Thr71),': [2129], 'employing': [2130], 'well-characterized': [2131], 'phospho-specific': [2132], 'antibodies': [2133, 3455], '(Fig': [2134, 2147, 2169, 2199, 2254, 2325, 2352, 2674, 2703, 2747, 2751, 2788, 2808, 2821, 3221, 3240, 3420, 3425, 3440, 3485, 3517, 3525, 3755, 3986, 4005, 4036, 4301], 'EV1).': [2135], 'Overexpression': [2136], 'significantly': [2139, 2787], 'both': [2141, 2641, 3305], '1A).': [2148, 2170, 2200, 2255, 2326], 'stimulated': [2150, 2761, 2815], '"enhanced': [2154], 'GTP-binding': [2155, 2252], 'mutants"': [2156], '(R1441C,': [2157], 'R1441G,': [2158], 'R1441H,': [2159], 'Y1699C)': [2160], 'consistent': [2189, 3247], 'state': [2194], 'Due': [2201], 'basal': [2205], 'mutant': [2209, 2649, 2698, 3793, 4264, 4281], 'displayed': [2210], 'elevated': [2211], 'absence': [2216, 2398], 'overexpression,': [2219], 'upon': [2224, 2467, 3120, 3194, 3507], 'overexpression.': [2226], 'I2020T,': [2228], 'T2031S,': [2229], 'G2385R': [2231], 'behaved': [2234], 'like': [2236], 'were': [2240, 2380, 2391, 2428, 2441, 2496, 2521, 2544, 2571, 2605, 2839, 2864, 2875, 3088, 3374, 3456, 3563, 3582, 3622, 3827, 3840, 3912, 3953, 4009, 4074, 4089, 4127], 'overexpression': [2244, 2341, 4300], 'lesser': [2247], 'general,': [2257], 'amount': [2259, 3444, 3981, 4175], 'correlates': [2263], 'activation;': [2269], 'however,': [2270], 'some': [2271], 'variation': [2272, 2317], 'correlating': [2273], 'level': [2276], 'observed.': [2281], 'Furthermore,': [2282], 'there': [2283, 2907, 2998], '2017)': [2296], 'conceivably,': [2298], 'may': [2301, 2710, 3448, 4041], 'slightly': [2303], 'different': [2304], 'preferences': [2307], 'proteins,': [2311, 4112], 'could': [2313, 4056], 'stimulation': [2331], 'induced': [2339, 2770], 'abolished': [2345], 'introducing': [2347], 'kinase-inactivating': [2349, 2557], 'D2017A': [2350, 2535, 2558], '1A,': [2353], 'right': [2354, 3620, 3773, 3838], 'panels),': [2355], 'confirming': [2356], 'enhancing': [2360], 'Click': [2367, 2823], 'here': [2368, 2824], 'expand': [2370, 2826], 'figure.': [2372, 2828, 4226], 'Figure': [2373, 2488, 2829, 3183, 3263, 3550, 3818, 4061, 4230, 4327], 'EV1.': [2374], 'Specificity': [2375], 'phospho-antibodies': [2377], 'transfected': [2381, 2497, 2840, 3285, 3564, 3575, 4075, 4082], 'LRRK2[G2091S]': [2383], 'LRRK2[S1292A,': [2385], 'G2019S].': [2386], '24': [2387, 2517, 2860, 3572, 4079], 'h': [2388, 2518, 2861, 3573, 4080], 'post-transfection,': [2389, 2519, 2862], 'treated': [2392, 3623, 3647, 3841], 'presence': [2395], '(+)': [2396], '(−)': [2399, 2512, 2853], 'MLi-2': [2404, 2470], '(100': [2405], 'nM,': [2406, 3629, 3651, 3855], '60': [2407], 'min)': [2408], 'lysed': [2409, 2522, 2865], 'analyzed': [2411, 2524, 2867, 2886, 3961], 'immunoblotting': [2413, 2444, 2456, 2526, 2869], 'antibodies.': [2417, 2530, 2873, 3607, 3975, 4144], 'As': [2418, 2551, 2577], '(A)': [2420, 2579, 2845, 2904, 3291], 'except': [2421, 2454, 2555, 2580], 'HA-tagged': [2425, 2514, 2857], 'LRRK2[Y1699C]': [2431], 'maximally': [2436], 'isoforms.': [2439], 'Lysates': [2440], 'subjected': [2442], 'anti-Rab29': [2447], 'phospho': [2448, 2460], 'Thr71': [2449, 2626], 'antibody.': [2450, 2462], 'Same': [2451], '(B)': [2453, 2848, 2996, 3294], 'anti-Rab10': [2459], 'No': [2463], 'signal': [2464], 'detected': [2466, 4025, 4128], 'phospho-residue': [2477], 'alanine.': [2480], 'WT,': [2481, 3908], 'wild': [2482], 'type.': [2483], 'Download': [2484, 2486, 2615, 2617, 3098, 3100, 3399, 3401, 3710, 3712, 3924, 3926, 4233, 4235], 'figure': [2485, 2616, 3099, 3400, 3711, 3925, 4234], 'PowerPoint': [2487, 2618, 3101, 3402, 3713, 3927, 4236], '1.': [2489], 'Left:': [2493], 'full-length': [2504, 4288], 'HA-empty': [2510, 2851, 2900, 2948, 3040], 'vector': [2511, 2852, 2901, 2949, 3041], '(+).': [2516], 'WT': [2531, 2905, 4072], 'corresponds': [2536], 'kinase-inactive': [2539], 'mutant.': [2541, 2568], 'Similar': [2542, 2569, 2603, 4007], 'results': [2543, 2570, 2604], 'two': [2547, 2574, 2608, 3091, 3364, 3887, 4189], 'separate': [2548, 2609, 3092], 'experiments.': [2549, 2576, 4190], 'Right:': [2550], 'left': [2553, 3775, 3836, 4118], 'panel': [2554], 'inserted': [2562], 'into': [2563, 3955, 4093], 'independent': [2575], 'LRRK2[R1441G]': [2582, 2652, 2750, 2792, 2847], 'variant': [2584], 'co-transfected': [2586], 'Rab29.': [2593], 'EE': [2594], 'indicates': [2595, 2600], 'Rab29[T71E,S72E]': [2596, 2697], 'AA': [2599], 'Rab29[T71A,S72A]': [2601, 2648], 'mutation.': [2602], 'experiments,': [2610, 3093], 'each': [2611, 3094, 3694, 3896], 'performed': [2612, 3095], 'duplicate.': [2614, 3097], 'test': [2620, 2894, 2937, 3029, 3945], 'Ser72': [2628], 'Ala.': [2643], 'still': [2650], 'same': [2655], 'ability': [2670, 2713], 'activate': [2672, 2701, 2715, 3543], '1B).': [2675, 2704], 'attempt': [2678, 4249], 'mimic': [2680], 'Glu': [2692], 'failed': [2699], 'This': [2705, 3487, 4038], 'suggests': [2706], 'decrease': [2711], 'selectively': [2718, 2832], 'next': [2722], 'evaluated': [2723], 'effect': [2725], '11': [2727], '(that': [2734], 'Rab29)': [2739], 'EV2A)': [2748], 'EV2B).': [2752, 2822], 'phosphorylation,': [2763], 'exception': [2766], 'modest': [2772], '~twofold': [2773], 'increase,': [2774], 'none': [2775], 'other': [2778, 2805], 'EV2A).': [2789], 'For': [2790, 2903, 2995, 3366, 3387], 'mutant,': [2793], 'increased': [2797, 3979], 'any': [2802], 'EV2B),': [2809], 'two-': [2818], 'threefold': [2820, 3997], 'EV2.': [2830], 'A,': [2835, 3277], 'B.': [2836, 3278], 'proteins.': [2859, 3794], 'Blots': [2874], 'quantified': [2876], 'LiCor': [2878], 'presented': [2880], 'average': [2882], '±': [2883, 3347, 3852, 4154, 4169], 'SEM,': [2884], 'using': [2887, 3749, 3971], 'one-way': [2888, 2918, 2931, 3010, 3023], 'ANOVA': [2889, 2932, 3024], "Dunnett's": [2891, 2934, 3026], 'multiple': [2892, 2935, 3027], 'comparison': [2893, 2936, 3028], 'comparing': [2895], 'groups': [2897, 2914, 2945, 3006, 3037], '(−).': [2902], 'statistically': [2910, 3002], 'difference': [2912, 2940, 3004, 3032], '(P': [2915, 3007, 3915, 4201], '=': [2916, 2922, 3008, 3014, 3353, 3361, 3670, 3673, 3899, 4192, 4195, 4198, 4202], '0.0135,': [2917], 'ANOVA,': [2919, 3011], 'F(11,': [2920, 3012], '12)': [2921, 3013], '3.911).': [2923], 'nsP': [2924, 3016], '>': [2925, 3017, 3688, 3890, 3916], '0.05,': [2926, 3018], '**P': [2927, 3352, 3672, 4191], '<': [2928, 3020, 3350], '0.01': [2929], 'mean': [2939, 3031, 3346], '95%': [2941, 3033], 'confidence': [2942, 3034], 'intervals': [2943, 3035], 'compared': [2946, 3038], 'control:': [2950, 3042], 'Rab1B': [2951, 3043], '−356.9': [2952], '332.6;': [2954], 'Rab5B': [2955, 3047], '−342.0': [2956], '347.6;': [2958], 'Rab7A': [2959, 3051], '−332.4': [2960], '357.2;': [2962], '−378.6': [2964], '311.0;': [2966], 'Rab8B': [2967, 3059], '−346.7': [2968], '342.9;': [2970], '−372.3': [2972], '317.3;': [2974], 'Rab12': [2975, 3067], '−499.8': [2976], '189.8;': [2978], '−865.3': [2980], '−175.7;': [2982], '−372.7': [2984], '316.8;': [2986], '−367.4': [2988], '322.2;': [2990], 'Rab39B': [2991, 3083], '−346.5': [2992], '343.1.': [2994], 'LRRK2[R1441G],': [2997], '0.0007,': [3009], '7.642).': [3015], '***P': [3019, 3669], '0.001': [3021], '−386.5': [3044], '411.2;': [3046], '−410.2': [3048], '387.5;': [3050], '−377.0': [3052], '420.7;': [3054], '−668.2': [3056], '129.6;': [3058], '−517.5': [3060], '280.3;': [3062], '−421.1': [3064], '376.7;': [3066], '−503.2': [3068], '294.6;': [3070], '−1,243': [3072], '−445.7;': [3074], '−433.5': [3076], '364.3;': [3078], '−548.2': [3080], '249.5;': [3082], '−390.4': [3084], '407.4.': [3086], 'membranes': [3107, 3119, 4004, 4153], 'At': [3108], 'steady': [3109], 'state,': [3110], 'primarily': [3113], 'cytosolic;': [3114], 'approximately': [3115], '10%': [3116, 4020], 'associates': [3117], 'cell': [3121, 3332], 'fractionation.': [3122], 'large': [3124], 'pool': [3125, 3135, 4040], 'cytoplasmic': [3127], 'obscures': [3129], 'membrane-associated': [3134, 3180, 3984], 'fixed': [3137, 3593], 'cells.': [3138], 'overcome': [3140], 'challenge,': [3142], 'avoid': [3145], 'possibility': [3147], 'spurious': [3149], 'precipitation': [3150], 'onto': [3155], 'cellular': [3156], 'structures': [3157], 'during': [3158], 'fixation,': [3159], 'employed': [3161], 'established': [3163], 'liquid': [3164, 3585], 'nitrogen': [3165, 3586], 'coverslip': [3166], 'freeze–thaw': [3167, 3587], 'protocol': [3168], '(Seaman,': [3169], '2004)': [3170], 'deplete': [3172, 3589], 'protein.': [3182, 3462, 3943], 'shows': [3185, 3307], 'R1441G': [3189, 3424, 3528, 3849, 3951, 4058], 'HeLa': [3192, 3281], 'transient': [3195], 'transfection.': [3196], 'localized': [3200, 3405], 'predominantly': [3201], 'perinuclear': [3204, 3227, 3388, 3446, 3505], 'distinct,': [3207], 'peripheral': [3208, 3367], 'punctae': [3209, 3235], 'detected,': [3212], '60%': [3214], 'contain': [3218], '2A': [3222], 'C).': [3224], 'region,': [3228], '40%': [3231], 'co-localized': [3236], 'Rab8': [3238, 3254, 3273], '2B': [3241], 'D).': [3243, 3520], 'fact': [3250], '2.': [3264], 'R1441G-LRRK2': [3265, 3286, 3324], 'co-localizes': [3266, 3801, 3810], 'periphery': [3271], 'nucleus': [3276], 'Shown': [3279], 'stained': [3283, 3595, 3828, 3858], '(red)': [3287, 3612, 3635], 'GFP-Rab10': [3290], 'GFP-Rab8': [3293], 'green.': [3296], 'Scale': [3297, 3315, 3706, 3920], 'bar,': [3298, 3316], '10': [3299, 3708, 3922], 'μm.': [3300, 3318, 3709, 3923], 'second': [3302], 'row': [3303], 'panels': [3306, 3621, 3839], 'portions': [3309], 'boxed': [3310], 'rows': [3313], 'above.': [3314], 'C,': [3319], 'D.': [3320], 'Percent': [3321, 3662], 'co-localization': [3322, 3477, 3614, 3640], 'regions': [3333], 'determined': [3335], "Mander's": [3338], 'coefficient': [3339], 'after': [3340], 'automatic': [3341], 'thresholding.': [3342], 'Error': [3343, 3680, 3882, 4184], 'bars': [3344, 3681, 3883, 4185], 'represent': [3345, 3492, 3682, 3884, 4042, 4057, 4186], 'SEM.': [3348], '****P': [3349, 4194], '0.0001;': [3351], '0.0076': [3354], "Student's": [3356, 3676, 3902, 4205], 'unpaired,': [3357, 3677, 3903, 4206], 'two-tailed': [3358, 3678, 3904, 4207], 't-test': [3359], '(n': [3360], '13': [3362], 'experiments).': [3365], 'quantitation,': [3368], 'boxes': [3369, 3393], 'size': [3372], 'generated': [3375, 4261], '(see': [3376, 3390, 3530, 4013], 'A)': [3377], 'included': [3379, 3394], 'plasma': [3381], 'excluded': [3384], 'nucleus.': [3386, 3398], 'quantitation': [3389], 'B),': [3391], 'half': [3395], 'complex': [3409], '(Wang': [3410], 'where': [3414], 'overlaps': [3416], 'p115': [3418, 3611], '3A).': [3421], 'Like': [3422], '2),': [3426], 'displays': [3430], 'distributed,': [3432], 'punctate': [3433, 3699], 'pattern': [3434], 'when': [3435, 3464], 'expressed': [3436, 4283], 'own': [3439], '3E).': [3441], 'small': [3443], 'co-localize': [3449, 3555], 'available': [3454, 4222], 'unable': [3457], 'label': [3459], 'showed': [3475], 'over': [3478], 'extended,': [3480], 'somewhat': [3481], 'perinuclear,': [3482], 'reticular': [3483], 'structure': [3484, 3488], '3B).': [3486], 'likely': [3490], 'disrupted': [3494], 'complex,': [3496], 'staining': [3498, 3700], 'became': [3499], 'concentrated': [3502], 'MLI-2': [3513, 3649, 3853], '3C': [3518], 'Co-localization': [3521], '3B)': [3526], 'Fig': [3531, 3769, 4014], '7H': [3532], 'below)': [3533], 'supports': [3536], 'can': [3542], 'Rab29-containing': [3548], 'membranes.': [3549, 3645], '3.': [3551], 'disperse': [3559], 'membranesHeLa': [3561], 'LRRK2-G2019S': [3566, 3570, 3660, 3696], 'Myc-Rab29': [3568, 3608, 3634, 4215], 'later': [3574, 4081], 'Myc-Rab29.': [3577, 4084], 'After': [3578, 4085], '48': [3579, 4086], 'h,': [3580, 4087], 'permeabilized': [3583], 'cytosol': [3590, 3958, 4094, 4167], 'then': [3592], 'mouse': [3597, 3599, 3743, 4135, 4137, 4139, 4142], 'anti-p115,': [3598], 'anti-Myc,': [3600], 'rabbit': [3602, 3605, 3830, 3860, 4130, 4132], 'anti-GFP': [3603], 'anti-LRRK2': [3606, 3972, 4133], '(green)': [3609, 3638, 3832, 3863], 'Golgi.': [3617], 'Left': [3618], 'without': [3626, 3844], 'MLI2': [3627, 3759, 3845], '(200': [3628, 3650, 3854], '4': [3630, 3652, 3856], 'h)': [3631, 3653, 3857], 'indicated.': [3633, 3847, 4115], 'eGFP-LRRK2-G2019S': [3637], 'dispersed': [3642], 'Rab29-labeled': [3643], 'Cells': [3646], 'compact,': [3655], 'Rab29-positive': [3656], 'Golgi,': [3657], '(green).': [3661], 'compact': [3666, 3762, 3875], 'staining;': [3668], '0.0002;': [3671], '0.002': [3674], 't-test.': [3679, 3905, 4208], 'SEM': [3683, 3885, 4187], 'three': [3685], 'experiments': [3686, 3888], '30': [3689], 'per': [3691, 3893], 'condition': [3692, 3894], 'experiment.': [3695, 3897], 'alone': [3697], 'showing': [3698, 3873], 'throughout': [3701], 'cell.': [3703], 'Data': [3704, 3918, 4182, 4228], 'information:': [3705, 3919, 4183], 'bars,': [3707, 3921], 'Disruption': [3714], 'previously': [3724], '2014),': [3733], 'light': [3735], 'microscopic': [3736], 'embryonic': [3744], 'fibroblasts': [3745], '(MEFs)': [3746], '(as': [3747], 'monitored': [3748], 'anti-GCC185': [3750, 3831, 3861], 'antibodies)': [3751], 'confirmed': [3752], 'finding': [3754], '4A': [3756], 'C);': [3758], 'restored': [3761], 'GCC185-stained': [3766], 'compartments': [3767], '(compare': [3768], '4B': [3770], 'C': [3772], 'panels).': [3776], 'Note': [3777, 4017], 'fragmentation': [3783], 'correlated': [3784], 'Together,': [3795], 'substrates,': [3804], 'Rab8,': [3807], 'important': [3813], 'key': [3814], 'activator,': [3815], 'GTPase.': [3817], '4.': [3819], 'LRRK2-R1441G': [3820, 4022, 4077, 4151], 'disrupts': [3822], 'morphology': [3824], 'Wild-type': [3825], 'MEFs': [3826], 'DAPI': [3834, 3865], '(blue);': [3835], 'Knock-in': [3848], 'MEF': [3850], 'antibody': [3862], '(blue).': [3866], 'Quantitation': [3867, 4145], 'percent': [3870], 'seen': [3879], '(A).': [3881], '50': [3891], '*P': [3898], '0.0184': [3900], 'Differences': [3906, 4209], 'WT+MLI2,': [3909], 'R1441G+MLI2': [3911], '0.5).': [3917], 'predicted': [3934], 'occur': [3936], 'surfaces': [3939], 'harboring': [3940], 'this,': [3946], 'expressing': [3948], 'fractionated': [3954, 4092], 'fractions': [3959, 4028, 4168], 'content': [3964], 'total': [3966, 3983, 4150, 4177], 'protein,': [3970], 'anti-pS1292': [3974], 'Expression': [3976], '5A': [3987], 'B)': [3989], 'led': [3992], 'enrichment': [3998], 'activated,': [4000], 'pS1292': [4001], '5C).': [4006], 'G2019S-LRRK2': [4012], '7': [4015], 'below).': [4016], 'about': [4019], '293': [4033], 'T': [4034], '5B).': [4037], 'Rab29-independent': [4039], 'another': [4047], 'Rab38,': [4054], 'aggregates.': [4060], '5.': [4062], 'LRRK2-R1441GHEK293T': [4068], 'Rab29−/−': [4069], '(KO)': [4070], 'harvested': [4090], 'fractions.': [4097], 'Immunoblot': [4098], '(75': [4102], 'μg)': [4103], '50%': [4106], 'equivalent': [4108], 'volume': [4109], '±Rab29': [4113], 'Numbers': [4116], 'indicate': [4119], 'mobility': [4120], 'marker': [4122], 'kDa;': [4125], 'anti-pS1292,': [4131], 'UDD3,': [4134], 'anti-LRRK2,': [4136], 'anti-LAMP2,': [4138], 'anti-tubulin,': [4140], 'anti-Myc': [4143], 'fraction': [4148], '(transfected': [4156], 'endogenous).': [4158], 'Amount': [4159], '(pS1292)': [4162], 'normalized': [4172], 'fraction.': [4181], '0.0025;': [4193], '0.00013;': [4196], 'ns': [4197], '0.1968)': [4203], 'KO': [4212], '(minus)': [4214], 'significant.': [4218], 'online': [4223], '5': [4231], '[embj201798099-sup-0002-SDataFig5.pdf]': [4232], 'Ankyrin': [4237, 4329], 'permit': [4240, 4332], 'initial': [4248], 'define': [4251], 'truncation': [4263], 'lacking': [4267], 'N-terminal,': [4269], '969': [4270], 'non-catalytic': [4271], 'encompassing': [4273], 'domains.': [4278], 'Although': [4279], 'lower': [4285], 'levels': [4286], 'clearly': [4295], '6A),': [4302], 'effector': [4307], 'fragment,': [4314], 'previous': [4321], 'study': [4322], '6.': [4328]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2771688344', 'counts_by_year': [{'year': 2024, 'cited_by_count': 21}, {'year': 2023, 'cited_by_count': 43}, {'year': 2022, 'cited_by_count': 55}, {'year': 2021, 'cited_by_count': 57}, {'year': 2020, 'cited_by_count': 75}, {'year': 2019, 'cited_by_count': 42}, {'year': 2018, 'cited_by_count': 20}], 'updated_date': '2024-12-08T15:29:36.075243', 'created_date': '2017-12-22'}
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