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Vesicle Docking Is a Key Target of Local PI(4,5)P2 Metabolism in the Secretory Pathway of INS-1 Cells. Cell Rep 2017 Aug 08;20(6):1409-1421

Date

08/10/2017

Pubmed ID

28793264

Pubmed Central ID

PMC5613661

DOI

10.1016/j.celrep.2017.07.041

Scopus ID

2-s2.0-85026870735 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) signaling is transient and spatially confined in live cells. How this pattern of signaling regulates transmitter release and hormone secretion has not been addressed. We devised an optogenetic approach to control PI(4,5)P2 levels in time and space in insulin-secreting cells. Combining this approach with total internal reflection fluorescence microscopy, we examined individual vesicle-trafficking steps. Unlike long-term PI(4,5)P2 perturbations, rapid and cell-wide PI(4,5)P2 reduction in the plasma membrane (PM) strongly inhibits secretion and intracellular Ca2+ concentration ([Ca2+]i) responses, but not sytaxin1a clustering. Interestingly, local PI(4,5)P2 reduction selectively at vesicle docking sites causes remarkable vesicle undocking from the PM without affecting [Ca2+]i. These results highlight a key role of local PI(4,5)P2 in vesicle tethering and docking, coordinated with its role in priming and fusion. Thus, different spatiotemporal PI(4,5)P2 signaling regulates distinct steps of vesicle trafficking, and vesicle docking may be a key target of local PI(4,5)P2 signaling in vivo.

Author List

Ji C, Fan F, Lou X

Author

Xuelin Lou PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Calcium Signaling
Cell Line
Cell Membrane
Insulin
Insulin-Secreting Cells
Phosphatidylinositol 4,5-Diphosphate
Rats
Secretory Pathway
Secretory Vesicles
Syntaxin 1