کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2828876 1570449 2010 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oligomeric structure of brain abundant proteins GAP-43 and BASP1
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Oligomeric structure of brain abundant proteins GAP-43 and BASP1
چکیده انگلیسی

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 (PIP2) 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 10–30 nm in diameter. BASP1 also formed higher aggregates of linear rod-like structure, with average length of about 100 nm. 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 PIP2 in functional clusters, which become accessible for other PIP2-binding proteins after dissociation of the oligomers.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 170, Issue 3, June 2010, Pages 470–483
نویسندگان
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