Abstract
CAPS (Calcium-dependent Activator Protein for Secretion, aka CADPS) and Munc13 (Mammalian Unc-13) proteins function to prime vesicles for Ca2+-triggered exocytosis in neurons and neuroendocrine cells. CAPS and Munc13 proteins contain conserved C-terminal domains that promote the assembly of SNARE complexes for vesicle priming. Similarities of the C-terminal domains of CAPS/Munc13 proteins with Complex Associated with Tethering Containing Helical Rods domains in multi-subunit tethering complexes (MTCs) have been reported. MTCs coordinate multiple interactions for SNARE complex assembly at constitutive membrane fusion steps. We review aspects of these diverse tethering and priming factors to identify common operating principles.
Highlights
CAPS and Munc13 proteins contain conserved C-terminal domains that promote the assembly of SNARE complexes for vesicle priming
The activity of CAPS in promoting SNARE complex formation was evident in studies www.frontiersin.org of SNARE-dependent liposome fusion where CAPS markedly increased the rate and extent of fusion between donor VAMP2 liposomes and syntaxin-1/SNAP-25 acceptor liposomes [105, 106]. These results suggested that CAPS acts to promote the insertion of the R-SNARE VAMP2 into Qabc-SNARE syntaxin1/SNAP-25 acceptors (Figure 1, lower) but it is not yet known if CAPS utilizes direct interactions with syntaxin-1/SNAP-25, with VAMP2, or with both to enable SNARE complex assembly
Munc13-4 promoted the fusion of VAMP2 donor liposomes with syntaxin1/SNAP-25 acceptor liposomes that was dependent on Ca2+ and Ca2+-binding residues in each C2 domain [120]. These results indicated that Ca2+-activated Munc13-4 can function to CAPS by promoting the recruitment of the R-SNARE VAMP2 into Qabc-SNARE syntaxin-1/SNAP-25 acceptors for RQaQbc-SNARE complex assembly
Summary
CAPS and Munc13 proteins contain conserved C-terminal domains that promote the assembly of SNARE complexes for vesicle priming. CATCHR domains in MTC subunits that possess them appear to generally mediate interactions with other subunits or with other proteins including SNAREs. One common theme illustrated by tethering factors at several vesicle trafficking stations is the ondemand assembly of Q-SNARE complexes with vesicle arrival.
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