biostudies-literatureTanaka YMEXT | Japan Society for the Promotion of ScienceJEOL, Ltd.MEXT | Japan Society for the Promotion of Science (JSPS)Uehara Memorial FoundationJapan IDDM networkOno Medical Research FoundationUehara Memorial Foundation (UMF)4777-4802https://www.ebi.ac.uk/biostudies/studies/S-EPMC11549326biostudies-literatureUnknown25(11)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 Ca_V1.2 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 Ca_V1.2 but not K_ir6.EMBO reportsKinesin-1 mediates proper ER folding of the Ca_V1.2 channel and maintains mouse glucose homeostasis.PMC11549326JP20K06634JP23000013 and JP16H06372N.A.Yang WTanaka YUeno HFarkhondeh AHirokawa NNoda MfalseKinesin-1 mediates proper ER folding of the Ca_V1.2 channel and maintains mouse glucose homeostasis.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 Ca_V1.2 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 Ca_V1.2 but not K_ir6.2024-01-01T00:00:00Z2024 Nov2026-06-01T17:34:08.599Z2025-04-06T18:25:24.652ZS-EPMC115493263932274010.1038/s44319-024-00246-y