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Regulation of SNARE Complex Assembly by Second Messengers

Roles of Phospholipases, Munc13 and Munc18

  • Chapter
Book cover Molecular Mechanisms of Exocytosis

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

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Abstract

Many specialized cell types are dedicated to the regulated exocytosis of biologically active substances. The secretory cargo is stored in vesicles, that have a low release probability in the absence of suitable secretory signals. Membrane fusion requires the assembly of soluble N-ethylmaleimide attachment protein receptor (SNARE) proteins into a trimeric SNARE complex, in mammals composed of syntaxin, SNAP-25/23 and synaptobrevin.1 Although SNARE complex assembly is sufficient to drive fusion of liposomes in cell-free systems, 2,3 spatially and temporally controlled membrane fusion in living cells requires the activity of accessory proteins. Such accessory proteins have been identified, for instance Muncl3 and Muncl8, that are essential for regulated secretion.

Here we review the molecular mechanisms by which Muncl3 and Muncl8 may regulate SNARE complex assembly. Regulatory mechanisms can be invoked by external signals such as ligand-receptor interactions, as well as by the local production of second messengers due to high secretory activity. All these routes are convergently reflected by central signaling molecules such as intracellular Ca2+, diacylglycerol, inositol-triphosphate or other phospholipase-generated products. Recently several novel pathways were described by which these molecules can provide regulatory feedback on the activity of Muncl3 and Muncl8 and hence, on SNARE-dependent exocytosis.

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Authors and Affiliations

  1. Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, De Boelelaan 1087, 1081 HV, Amsterdam, The Netherlands

    Alexander J. A. Groffen

  2. Department of Functional Genomics Center for Neurogenomics and Cognition Research, Vrije Universiteit (VU) and VU Medical Centre, Amsterdam, The Netherlands

    Matthijs Verhage

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  1. Alexander J. A. Groffen
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  2. Matthijs Verhage
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Groffen, A.J.A., Verhage, M. (2007). Regulation of SNARE Complex Assembly by Second Messengers. In: Molecular Mechanisms of Exocytosis. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-39961-4_2

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