Reconciling the regulatory role of Munc18 proteins in SNARE-complex assembly
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Author(s)
Rehman, Asma
Archbold, Julia K
Hu, Shu-Hong
Norwood, Suzanne J
Collins, Brett M
Martin, Jennifer L
Griffith University Author(s)
Year published
2014
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Show full item recordAbstract
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-ethylmaleimidesensitive
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 ...
View more >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-ethylmaleimidesensitive 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.
View less >
View more >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-ethylmaleimidesensitive 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.
View less >
Journal Title
IU Cr J
Volume
1
Funder(s)
NHMRC
Grant identifier(s)
APP1066069
Copyright Statement
© 2014 This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Subject
Condensed matter physics
Physical chemistry
Biochemistry and cell biology not elsewhere classified