A conserved regulatory mode in exocytic membrane fusion revealed by Mso1p membrane interactions

M. Weber-Boyvat, H. Zhao, Nina Aro, Q. Yuan, K. Chernov, J. Peränen, P. Lappalainen, Jussi Jäntti

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2 Citations (Scopus)

Abstract

Sec1/Munc18 family proteins are important components of soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complex–mediated membrane fusion processes. However, the molecular interactions and the mechanisms involved in Sec1p/Munc18 control and SNARE complex assembly are not well understood. We provide evidence that Mso1p, a Sec1p- and Sec4p-binding protein, interacts with membranes to regulate membrane fusion. We identify two membrane-binding sites on Mso1p. The N-terminal region inserts into the lipid bilayer and appears to interact with the plasma membrane, whereas the C-terminal region of the protein binds phospholipids mainly through electrostatic interactions and may associate with secretory vesicles. The Mso1p membrane interactions are essential for correct subcellular localization of Mso1p–Sec1p complexes and for membrane fusion in Saccharomyces cerevisiae. These characteristics are conserved in the phosphotyrosine-binding (PTB) domain of β-amyloid precursor protein–binding Mint1, the mammalian homologue of Mso1p. Both Mint1 PTB domain and Mso1p induce vesicle aggregation/clustering in vitro, supporting a role in a membrane-associated process. The results identify Mso1p as a novel lipid-interacting protein in the SNARE complex assembly machinery. Furthermore, our data suggest that a general mode of interaction, consisting of a lipid-binding protein, a Rab family GTPase, and a Sec1/Munc18 family protein, is important in all SNARE-mediated membrane fusion events.
Original languageEnglish
Pages (from-to)331-341
Number of pages11
JournalMolecular Biology of the Cell
Volume24
Issue number3
DOIs
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed

Fingerprint

Membrane Fusion
Membranes
Munc18 Proteins
Phosphotyrosine
Proteins
Carrier Proteins
rab GTP-Binding Proteins
Lipids
Secretory Vesicles
Lipid Bilayers
Static Electricity
Amyloid
Cluster Analysis
Saccharomyces cerevisiae
Phospholipids
Binding Sites
Cell Membrane

Cite this

Weber-Boyvat, M. ; Zhao, H. ; Aro, Nina ; Yuan, Q. ; Chernov, K. ; Peränen, J. ; Lappalainen, P. ; Jäntti, Jussi. / A conserved regulatory mode in exocytic membrane fusion revealed by Mso1p membrane interactions. In: Molecular Biology of the Cell. 2013 ; Vol. 24, No. 3. pp. 331-341.
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abstract = "Sec1/Munc18 family proteins are important components of soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complex–mediated membrane fusion processes. However, the molecular interactions and the mechanisms involved in Sec1p/Munc18 control and SNARE complex assembly are not well understood. We provide evidence that Mso1p, a Sec1p- and Sec4p-binding protein, interacts with membranes to regulate membrane fusion. We identify two membrane-binding sites on Mso1p. The N-terminal region inserts into the lipid bilayer and appears to interact with the plasma membrane, whereas the C-terminal region of the protein binds phospholipids mainly through electrostatic interactions and may associate with secretory vesicles. The Mso1p membrane interactions are essential for correct subcellular localization of Mso1p–Sec1p complexes and for membrane fusion in Saccharomyces cerevisiae. These characteristics are conserved in the phosphotyrosine-binding (PTB) domain of β-amyloid precursor protein–binding Mint1, the mammalian homologue of Mso1p. Both Mint1 PTB domain and Mso1p induce vesicle aggregation/clustering in vitro, supporting a role in a membrane-associated process. The results identify Mso1p as a novel lipid-interacting protein in the SNARE complex assembly machinery. Furthermore, our data suggest that a general mode of interaction, consisting of a lipid-binding protein, a Rab family GTPase, and a Sec1/Munc18 family protein, is important in all SNARE-mediated membrane fusion events.",
author = "M. Weber-Boyvat and H. Zhao and Nina Aro and Q. Yuan and K. Chernov and J. Per{\"a}nen and P. Lappalainen and Jussi J{\"a}ntti",
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A conserved regulatory mode in exocytic membrane fusion revealed by Mso1p membrane interactions. / Weber-Boyvat, M.; Zhao, H.; Aro, Nina; Yuan, Q.; Chernov, K.; Peränen, J.; Lappalainen, P.; Jäntti, Jussi.

In: Molecular Biology of the Cell, Vol. 24, No. 3, 2013, p. 331-341.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Weber-Boyvat, M.

AU - Zhao, H.

AU - Aro, Nina

AU - Yuan, Q.

AU - Chernov, K.

AU - Peränen, J.

AU - Lappalainen, P.

AU - Jäntti, Jussi

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N2 - Sec1/Munc18 family proteins are important components of soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complex–mediated membrane fusion processes. However, the molecular interactions and the mechanisms involved in Sec1p/Munc18 control and SNARE complex assembly are not well understood. We provide evidence that Mso1p, a Sec1p- and Sec4p-binding protein, interacts with membranes to regulate membrane fusion. We identify two membrane-binding sites on Mso1p. The N-terminal region inserts into the lipid bilayer and appears to interact with the plasma membrane, whereas the C-terminal region of the protein binds phospholipids mainly through electrostatic interactions and may associate with secretory vesicles. The Mso1p membrane interactions are essential for correct subcellular localization of Mso1p–Sec1p complexes and for membrane fusion in Saccharomyces cerevisiae. These characteristics are conserved in the phosphotyrosine-binding (PTB) domain of β-amyloid precursor protein–binding Mint1, the mammalian homologue of Mso1p. Both Mint1 PTB domain and Mso1p induce vesicle aggregation/clustering in vitro, supporting a role in a membrane-associated process. The results identify Mso1p as a novel lipid-interacting protein in the SNARE complex assembly machinery. Furthermore, our data suggest that a general mode of interaction, consisting of a lipid-binding protein, a Rab family GTPase, and a Sec1/Munc18 family protein, is important in all SNARE-mediated membrane fusion events.

AB - Sec1/Munc18 family proteins are important components of soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complex–mediated membrane fusion processes. However, the molecular interactions and the mechanisms involved in Sec1p/Munc18 control and SNARE complex assembly are not well understood. We provide evidence that Mso1p, a Sec1p- and Sec4p-binding protein, interacts with membranes to regulate membrane fusion. We identify two membrane-binding sites on Mso1p. The N-terminal region inserts into the lipid bilayer and appears to interact with the plasma membrane, whereas the C-terminal region of the protein binds phospholipids mainly through electrostatic interactions and may associate with secretory vesicles. The Mso1p membrane interactions are essential for correct subcellular localization of Mso1p–Sec1p complexes and for membrane fusion in Saccharomyces cerevisiae. These characteristics are conserved in the phosphotyrosine-binding (PTB) domain of β-amyloid precursor protein–binding Mint1, the mammalian homologue of Mso1p. Both Mint1 PTB domain and Mso1p induce vesicle aggregation/clustering in vitro, supporting a role in a membrane-associated process. The results identify Mso1p as a novel lipid-interacting protein in the SNARE complex assembly machinery. Furthermore, our data suggest that a general mode of interaction, consisting of a lipid-binding protein, a Rab family GTPase, and a Sec1/Munc18 family protein, is important in all SNARE-mediated membrane fusion events.

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