Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion
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Date
2016-08-15
Publication Type
Journal Article
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Abstract
Membrane fusion is essential for eukaryotic life, requiring SNARE proteins to zipper up in an α-helical bundle to pull two membranes together. Here, we show that vesicle fusion can be suppressed by phosphorylation of core conserved residues inside the SNARE domain. We took a proteomics approach using a PKCB knockout mast cell model and found that the key mast cell secretory protein VAMP8 becomes phosphorylated by PKC at multiple residues in the SNARE domain. Our data suggest that VAMP8 phosphorylation reduces vesicle fusion in vitro and suppresses secretion in living cells, allowing vesicles to dock but preventing fusion with the plasma membrane. Markedly, we show that the phosphorylation motif is absent in all eukaryotic neuronal VAMPs, but present in all other VAMPs. Thus, phosphorylation of SNARE domains is a general mechanism to restrict how much cells secrete, opening the door for new therapeutic strategies for suppression of secretion.
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published
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Journal / series
Volume
35 (16)
Pages / Article No.
1810 - 1821
Publisher
Wiley
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Subject
Mast cell degranulation; Protein kinase C; Secretion; SNARE complex; VAMP8