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Review
. 2013 Dec 4:4:187.
doi: 10.3389/fendo.2013.00187.

CAPS and Munc13: CATCHRs that SNARE Vesicles

Declan J James  1 , Thomas F J Martin  1
Affiliations
Review

CAPS and Munc13: CATCHRs that SNARE Vesicles

Declan J James et al. Front Endocrinol (Lausanne). .

Abstract

CAPS (Calcium-dependent Activator Protein for Secretion, aka CADPS) and Munc13 (Mammalian Unc-13) proteins function to prime vesicles for Ca(2+)-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.

Keywords: CAPS (aka CADPS); Munc13; SNAREs; multi-subunit tethering complexes; priming factors; vesicle fusion.

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Figures

Figure 1
Figure 1
Upper panel: schematic of priming factor (CAPS, Munc13) and tethering complex (exocyst, Dsl1, HOPS) composition and interactions. Multi-domain CAPS and Munc13 proteins interact with neuronal SNAREs and PIP2 and co-function with the SM Munc18-1. The exocyst complex with eight subunits interacts with cognate SNAREs, PIP2, and the SM Sec1. The Dsl1 complex with three subunits interacts with cognate SNAREs and co-functions with the SM protein Sly1. The HOPS complex with six subunits interacts with cognate SNAREs, PI3P, and PIP2, and contains the SM protein Vps33. Lower panel: schematic of CAPS function in vesicle priming depicting (i) PH domain binding to PIP2 and (ii) MHD1-mediated SNARE binding. Simultaneous binding of vesicle and plasma membrane constituents by CAPS might tether vesicles (A) in proximity to the SNARE proteins. These interactions could lead to (iii) syntaxin-1/SNAP-25 heterodimer formation followed by VAMP2 insertion to form trans-SNARE complexes in priming (B). (iv) Full SNARE complex zippering in response to elevations of intracellular calcium mediated by synaptotagmin and complexin triggers vesicle fusion (C) and contents release into the extracellular space.
Figure 2
Figure 2
Schematic of CAPS/Munc13 family of priming factors. Colored boxes indicate relative location of C2, C1, PH, MHD1, and MHD2 domains. The CATCHR homology region is indicated by black line.
See this image and copyright information in PMC

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