Kinesin-1 mediates proper ER folding of the CaV1.2 channel and maintains mouse glucose homeostasis

ABSTRACT: Glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells is a principal mechanism for systemic glucose homeostasis, of which regulatory mechanisms are still unclear. Here we show that kinesin molecular motor KIF5B is essential for GSIS through maintaining the voltage-gated calcium channel CaV1.2 levels, by facilitating an Hsp70-to-Hsp90 chaperone exchange to pass through the quality control in the endoplasmic reticulum (ER). Phenotypic analyses of KIF5B conditional knockout (cKO) mouse beta cells revealed significant abolishment of glucose-stimulated calcium transients, which altered the behaviors of insulin granules via abnormally stabilized cortical F-actin. KIF5B and Hsp90 colocalize to microdroplets on ER sheets, where CaV1.2 but not Kir6.2 is accumulated. In the absence

SUBMITTER: Yosuke Tanaka 

PROVIDER: S-SCDT-10_1038-S44319-024-00246-Y | biostudies-other |

REPOSITORIES: biostudies-other