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Publication : CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions.

First Author  James DJ Year  2009
Journal  Proc Natl Acad Sci U S A Volume  106
Issue  41 Pages  17308-13
PubMed ID  19805029 Mgi Jnum  J:248215
Mgi Id  MGI:6092627 Doi  10.1073/pnas.0900755106
Citation  James DJ, et al. (2009) CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions. Proc Natl Acad Sci U S A 106(41):17308-13
abstractText  Ca(2+)-dependent activator protein for secretion (CAPS) is an essential factor for regulated vesicle exocytosis that functions in priming reactions before Ca(2+)-triggered fusion of vesicles with the plasma membrane. However, the precise events that CAPS regulates to promote vesicle fusion are unclear. In the current work, we reconstituted CAPS function in a SNARE-dependent liposome fusion assay using VAMP2-containing donor and syntaxin-1/SNAP-25-containing acceptor liposomes. The CAPS stimulation of fusion required PI(4,5)P(2) in acceptor liposomes and was independent of Ca(2+), but Ca(2+) dependence was restored by inclusion of synaptotagmin. CAPS stimulated trans-SNARE complex formation concomitant with the stimulation of full membrane fusion at physiological SNARE densities. CAPS bound syntaxin-1, and CAPS truncations that competitively inhibited syntaxin-1 binding also inhibited CAPS-dependent fusion. The results revealed an unexpected activity of a priming protein to accelerate fusion by efficiently promoting trans-SNARE complex formation. CAPS may function in priming by organizing SNARE complexes on the plasma membrane.
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