演題：Priming factors prepare SNAREs for calcium-triggered vesicle fusion
講演要旨：SNARE protein complexes between VAMP2 on vesicles and
syntaxin-1/SNAP25 on the plasma membrane mediate the final
steps of vesicle fusion triggered by Ca2+.
However&s_comma; the pathway of SNARE complex assembly prior to fusion and the
factors that catalyze it are poorly understood. A stage of vesicle
exocytosis termed priming establishes whether vesicles are competent
for Ca2+-triggered fusion. Several protein factors that operate
in priming have been identified including CAPS and Munc13 proteins.
The phospholipid PI-4&s_comma;5-P2 is also essential and its (re)synthesis
represents an ATP-dependent stage of priming. We found that CAPS
accelerates SNARE-dependent liposome fusion in vitro that is
dependent upon PI-4&s_comma;5-P2 and a functional PH domain in CAPS.
CAPS promoted trans SNARE complex formation probably through its direct
interactions with syntaxin and SNAP25. SNARE binding was found
to be mediated by a CAPS domain (MH) that is conserved among
CAPS/Munc13 family members.
The MH domain binds directly to helical SNARE domains.
Our findings on CAPS are being generalized to Munc13 family members.
Current studies are directed toward determining how CAPS promotes SNARE
These studies will reveal the pathway by which SNARE complex assembly
occurs&s_comma; and will provide clarification of the priming step
in vesicle fusion.
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