Title: Strategies in Regulation of Protein Associations of the Spectrin-Based Membrane Skeleton
Abstract: The spectrin-based membrane skeleton of nonerythroid cells exhibits an unsuspected variety in protein interactions and regulatory mechanisms. Spectrin has at least two options in linkage to the membrane: ankyrin-mediated interaction with integral membrane proteins and direct linkages with ankyrin-independent sites. Ankyrin includes at least two families of functionally distinct isoforms, a general isoform expressed in many cells and a specialized isoform expressed in a limited number of cells and localized in a highly polarized distribution in these cells. Proteins likely to associate with the specialized isoforms of ankyrin based on association in vitro assays and co-localization in cells include the anion exchanger of erythrocytes and collecting ducts of kidney, the Na/K ATPase in distal tubule cells of kidney, and the voltage-dependent sodium channel in neuron. An additional mechanism for ankyrin diversity is processed variants of ankyrin with deleted regulatory domains that express binding sites unavailable to unprocessed ankyrinc Spectrin also can interact with high affinity with protein sites in synaptosomes and other membranes that are independent of ankyrin. Calmodulin in the presence of submicromolar concentrations of calcium is a competitive inhibitor of direct binding of spectrin to synaptosomal membranes but does not affect spectrin-ankyrin interactions. Thus the potential exists for differential regulation of spectrin-membrane interactions. The assembly state of the spectrin-actin lattice may also vary in certain cells. Adducin, a protein that promotes spectrin-actin interactions, is concentrated at sites of cell-cell contact in certain epithelial cells. These studies provide a low-resolution view of the spectrin skeleton and emphasize the possibilities for participation of this structure in a variety of functions including maintenance of specialized cell domains and participation in dynamic calcium-regulated processes.
Publication Year: 1989
Publication Date: 1989-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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