| Autor: |
Xie B; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden., Nguyen PM; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden., Idevall-Hagren O; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. |
| Jazyk: |
angličtina |
| Zdroj: |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2019 Apr; Vol. 33 (4), pp. 4716-4728. Date of Electronic Publication: 2018 Dec 27. |
| DOI: |
10.1096/fj.201801878R |
| Abstrakt: |
Endoplasmic reticulum (ER)-plasma membrane (PM) contacts are dynamic structures with important roles in the regulation of calcium (Ca 2 + ) and lipid homeostasis. The extended synaptotagmins (E-Syts) are ER-localized lipid transport proteins that interact with PM phosphatidylinositol 4,5-bisphosphate in a Ca 2+ -dependent manner. E-Syts bidirectionally transfer glycerolipids, including diacylglycerol (DAG), between the 2 juxtaposed membranes, but the biologic significance of this transport is still unclear. Using insulin-secreting cells and live-cell imaging, we now show that Ca 2+ -triggered exocytosis of insulin granules is followed, in sequence, by PM DAG formation and E-Syt1 recruitment. E-Syt1 counteracted the depolarization-induced DAG formation through a mechanism that required both voltage-dependent Ca 2+ influx and Ca 2+ release from the ER. E-Syt1 knockdown resulted in prolonged accumulation of DAG in the PM, resulting in increased glucose-stimulated insulin secretion. We conclude that Ca 2+ -triggered exocytosis is temporally coupled to Ca 2+ -triggered E-Syt1 PM recruitment and removal of DAG to negatively regulate the same process.-Xie, B., Nguyen, P. M., Idevall-Hagren, O. Feedback regulation of insulin secretion by extended synaptotagmin-1. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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