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  • Local activation of focal adhesion kinase orchestrates the positioning of presynaptic scaffold proteins and Ca2+ signalling to control glucose-dependent insulin secretion.

Local activation of focal adhesion kinase orchestrates the positioning of presynaptic scaffold proteins and Ca2+ signalling to control glucose-dependent insulin secretion.

eLife (2022-05-14)
Dillon Jevon, Kylie Deng, Nicole Hallahan, Krish Kumar, Jason Tong, Wan Jun Gan, Clara Tran, Marcela Bilek, Peter Thorn
RESUMEN

A developing understanding suggests that spatial compartmentalisation in pancreatic β cells is critical in controlling insulin secretion. To investigate the mechanisms, we have developed live-cell subcellular imaging methods using the mouse organotypic pancreatic slice. We demonstrate that the organotypic pancreatic slice, when compared with isolated islets, preserves intact β-cell structure, and enhances glucose-dependent Ca2+ responses and insulin secretion. Using the slice technique, we have discovered the essential role of local activation of integrins and the downstream component, focal adhesion kinase (FAK), in regulating β cells. Integrins and FAK are exclusively activated at the β-cell capillary interface and using in situ and in vitro models we show their activation both positions presynaptic scaffold proteins, like ELKS and liprin, and regulates glucose-dependent Ca2+ responses and insulin secretion. We conclude that FAK orchestrates the final steps of glucose-dependent insulin secretion within the restricted domain where β-cell contact the islet capillaries.

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Sigma-Aldrich
Monoclonal Anti-Talin antibody produced in mouse, clone 8d4, ascites fluid
Sigma-Aldrich
Anticuerpo anti-división del homólogo 3 defectuoso, Upstate®, from rabbit
Sigma-Aldrich
Anti-ELKS antibody, Mouse monoclonal, clone ELKS-30, purified from hybridoma cell culture