Septin dynamics are essential for exocytosis
In: The Journal of biological chemistry, Jg. 290 (2015-01-11), Heft 9
Online
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Zugriff:
Septins are a family of 14 cytoskeletal proteins that dynamically form hetero-oligomers and organize membrane microdomains for protein complexes. The previously reported interactions with SNARE proteins suggested the involvement of septins in exocytosis. However, the contradictory results of up- or down-regulation of septin-5 in various cells and mouse models or septin-4 in mice suggested either an inhibitory or a stimulatory role for these septins in exocytosis. The involvement of the ubiquitously expressed septin-2 or general septin polymerization in exocytosis has not been explored to date. Here, by nano-LC with tandem MS and immunoblot analyses of the septin-2 interactome in mouse brain, we identified not only SNARE proteins but also Munc-18-1 (stabilizes assembled SNARE complexes), N-ethylmaleimide-sensitive factor (NSF) (disassembles SNARE complexes after each membrane fusion event), and the chaperones Hsc70 and synucleins (maintain functional conformation of SNARE proteins after complex disassembly). Importantly, α-soluble NSF attachment protein (SNAP), the adaptor protein that mediates NSF binding to the SNARE complex, did not interact with septin-2, indicating that septins undergo reorganization during each exocytosis cycle. Partial depletion of septin-2 by siRNA or impairment of septin dynamics by forchlorfenuron inhibited constitutive and stimulated exocytosis of secreted and transmembrane proteins in various cell types. Forchlorfenuron impaired the interaction between SNAP-25 and its chaperone Hsc70, decreasing SNAP-25 levels in cultured neuroendocrine cells, and inhibited both spontaneous and stimulated acetylcholine secretion in mouse motor neurons. The results demonstrate a stimulatory role of septin-2 and the dynamic reorganization of septin oligomers in exocytosis.
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Septin dynamics are essential for exocytosis
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Autor/in / Beteiligte Person: | Marcus, Elizabeth A. ; Bukharaeva, Ellya ; Whitelegge, Julian P. ; Capri, Joe ; Tokhtaeva, Elmira ; Deiss-Yehiely, Nimrod ; Khuzakhmetova, Venera ; Dada, Laura A. ; Sachs, George ; Vagin, Olga ; Fernandez-Salas, Ester |
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Zeitschrift: | The Journal of biological chemistry, Jg. 290 (2015-01-11), Heft 9 |
Veröffentlichung: | 2015 |
Medientyp: | unknown |
ISSN: | 1083-351X (print) |
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