title: Reconciling the regulatory role of Munc18 proteins in SNARE-complex assembly.
abstract: Membrane fusion is essential for human health, playing a vital role in processes as diverse as neurotransmission and blood glucose control. Two protein families are key: (1) the Sec1p/Munc18 (SM) and (2) the soluble N-ethylmaleimide-sensitive attachment protein receptor (SNARE) proteins. Whilst the essential nature of these proteins is irrefutable, their exact regulatory roles in membrane fusion remain controversial. In particular, whether SM proteins promote and/or inhibit the SNARE-complex formation required for membrane fusion is not resolved. Crystal structures of SM proteins alone and in complex with their cognate SNARE proteins have provided some insight, however, these structures lack the transmembrane spanning regions of the SNARE proteins and may not accurately reflect the native state. Here, we review the literature surrounding the regulatory role of mammalian Munc18 SM proteins required for exocytosis in eukaryotes. Our analysis suggests that the conflicting roles reported for these SM proteins may reflect differences in experimental design. SNARE proteins appear to require C-terminal immobilization or anchoring, for example through a transmembrane domain, to form a functional fusion complex in the presence of Munc18 proteins.
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Asma
authors.initials: A
authors.lastname: Rehman
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Archbold
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Hu
authors.affiliation: Division of Molecular Cell Biology, Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Norwood
authors.affiliation: Division of Molecular Cell Biology, Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Collins
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martin
keywords: Munc18; SM proteins; SNARE proteins; membrane trafficking; syntaxin