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TRPM7 facilitates cholinergic vesicle fusion with the plasma membrane #MMPMID18539771
Brauchi S; Krapivinsky G; Krapivinsky L; Clapham DE
Proc Natl Acad Sci U S A 2008[Jun]; 105 (24): 8304-8 PMID18539771show ga
TRPM7, of the transient receptor potential (TRP) family, is both an ion channel and a kinase. Previously, we showed that TRPM7 is located in the membranes of acetylcholine (ACh)-secreting synaptic vesicles of sympathetic neurons, forms a molecular complex with proteins of the vesicular fusion machinery, and is critical for stimulated neurotransmitter release. Here, we targeted pHluorin to small synaptic-like vesicles (SSLV) in PC12 cells and demonstrate that it can serve as a single-vesicle plasma membrane fusion reporter. In PC12 cells, as in sympathetic neurons, TRPM7 is located in ACh-secreting SSLVs. TRPM7 knockdown by siRNA, or abolishing channel activity by expression of a dominant negative TRPM7 pore mutant, decreased the frequency of spontaneous and voltage-stimulated SSLV fusion events without affecting large dense core vesicle secretion. We conclude that the conductance of TRPM7 across the vesicle membrane is important in SSLV fusion.
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Proc+Natl+Acad+Sci+U+S+A 2008 ; 105 (24): 8304-8
