Evidence that electrostatic interactions between vesicle-associated membrane protein 2 and acidic phospholipids may modulate the fusion of transport vesicles with the plasma membrane

Dumaine Williams, Jérome Vicôgne, Irina Zaitseva, Stuart McLaughlin, Jeffrey E. Pessin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The juxtamembrane domain of vesicle-associated membrane protein (VAMP) 2 (also known as synaptobrevin2) contains a conserved cluster of basic/hydrophobic residues that may play an important role in membrane fusion. Our measurements on peptides corresponding to this domain determine the electrostatic and hydrophobic energies by which this domain of VAMP2 could bind to the adjacent lipid bilayer in an insulin granule or other transport vesicle. Mutation of residues within the juxtamembrane domain that reduce the VAMP2 net positive charge, and thus its interaction with membranes, inhibits secretion of insulin granules in β cells. Increasing salt concentration in permeabilized cells, which reduces electrostatic interactions, also results in an inhibition of insulin secretion. Similarly, amphipathic weak bases (e.g., sphingosine) that reverse the negative electrostatic surface potential of a bilayer reverse membrane binding of the positively charged juxtamembrane domain of a reconstituted VAMP2 protein and inhibit membrane fusion. We propose a model in which the positively charged VAMP and syntaxin juxtamembrane regions facilitate fusion by bridging the negatively charged vesicle and plasma membrane leaflets.

Original languageEnglish (US)
Pages (from-to)4910-4919
Number of pages10
JournalMolecular Biology of the Cell
Volume20
Issue number23
DOIs
StatePublished - 2009

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Vesicle-Associated Membrane Protein 2
Transport Vesicles
Static Electricity
Phospholipids
Cell Membrane
Insulin
Membrane Fusion Proteins
R-SNARE Proteins
Qa-SNARE Proteins
Membrane Fusion
Sphingosine
Membranes
Lipid Bilayers
Salts
Peptides
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Evidence that electrostatic interactions between vesicle-associated membrane protein 2 and acidic phospholipids may modulate the fusion of transport vesicles with the plasma membrane. / Williams, Dumaine; Vicôgne, Jérome; Zaitseva, Irina; McLaughlin, Stuart; Pessin, Jeffrey E.

In: Molecular Biology of the Cell, Vol. 20, No. 23, 2009, p. 4910-4919.

Research output: Contribution to journalArticle

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AU - Pessin, Jeffrey E.

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