| First Author | Zhang K | Year | 2021 |
| Journal | Mol Cell Endocrinol | Volume | 520 |
| Pages | 111076 | PubMed ID | 33159991 |
| Mgi Jnum | J:303650 | Mgi Id | MGI:6510750 |
| Doi | 10.1016/j.mce.2020.111076 | Citation | Zhang K, et al. (2021) CASK, APBA1, and STXBP1 collaborate during insulin secretion. Mol Cell Endocrinol 520:111076 |
| abstractText | Calcium/calmodulin-dependent serine protein kinase (CASK) knockdown reduces insulin vesicle docking to cell membranes. Here, we explored CASK interactions with other proteins during insulin secretion. Using co-immunoprecipitation, liquid chromatography-mass spectrometry and bioinformatic analysis, we identified that CASK, Adapter protein X11 alpha (APBA1), and Syntaxin binding protein 1 (STXBP1) formed tripartite complex during insulin secretion. CASK enhanced APBA1-STXBP1 interaction and mediated their traffic from cytoplasm to plasma membrane during insulin release. High fatty acid stimulation decreased insulin secretion along with CASK, APBA1, and STXBP1 expression; Cask overexpression enhanced CASK/APBA1/STXBP1 tripartite complex function, and may thereby rescue lipotoxicity-induced insulin-release defects. Collectively, our results illustrated the function of CASK in insulin granules exocytosis, which broadens the underlying mechanism of insulin secretion and highlights the clinical potential of CASK as a drug target of type 2 Diabetes Mellitus (T2DM). |
