Oligomeric structure of brain abundant proteins GAP-43 and BASP1.

J Struct Biol

Division of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute of Russian Academy of Sciences, 188300 Gatchina, Leningrad District, Russia.

Published: June 2010

Brain abundant proteins GAP-43 and BASP1 participate in the regulation of actin cytoskeleton dynamics in neuronal axon terminals. The proposed mechanism suggests that the proteins sequester phosphatidylinositol-4,5-diphosphate (PIP(2)) in the inner leaflet of the plasma membrane. We found that model anionic phospholipid membranes in the form of liposomes induce rapid oligomerization of GAP-43 and BASP1 proteins. Multiply charged phosphoinositides produced the most potent effect. Anionic detergent sodium dodecyl sulfate (SDS) at submicellar concentration stimulated formation of similar oligomers in solution. BASP1, but not GAP-43, also formed oligomers at sufficiently high concentration in the absence of lipids and SDS. Electron microscopy study demonstrated that the oligomers have disk-shaped or annular structure of 10-30nm in diameter. BASP1 also formed higher aggregates of linear rod-like structure, with average length of about 100nm. In outward appearance, the oligomers and linear aggregates are reminiscent of oligomers and protofibrils of amyloid proteins. Both the synthetic N-terminal peptide GAP-43(1-40) and the brain-derived fragment GAP-43-3 preserved the ability to oligomerize under the action of acidic phospholipids and SDS. On the contrary, BASP1 fragment truncated by the short N-terminal myristoylated peptide was unable to form oligomers. GAP-43 and BASP1 oligomerization can be regulated by calmodulin, which disrupts the oligomers and displaces the proteins from the membrane. We suggest that in vivo, the role of membrane-bound GAP-43 and BASP1 oligomers consists in accumulation of PIP(2) in functional clusters, which become accessible for other PIP(2)-binding proteins after dissociation of the oligomers.

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http://dx.doi.org/10.1016/j.jsb.2010.01.010DOI Listing

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