| First Author | Pan JY | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 51 | Pages | 26352-26363 |
| PubMed ID | 27624941 | Mgi Jnum | J:237641 |
| Mgi Id | MGI:5816404 | Doi | 10.1074/jbc.M116.727990 |
| Citation | Pan JY, et al. (2016) Regulation of L-type Ca2+ Channel Activity and Insulin Secretion by Huntingtin-associated Protein 1. J Biol Chem 291(51):26352-26363 |
| abstractText | Huntingtin-associated protein 1 (Hap1) was originally identified as a protein that binds to the Huntington disease protein, huntingtin. Growing evidence has shown that Hap1 participates in intracellular trafficking via its association with various microtubule-dependent transporters and organelles. Recent studies also revealed that Hap1 is involved in exocytosis such as insulin release from pancreatic beta-cells. However, the mechanism underlying the action of Hap1 on insulin release remains to be investigated. We found that Hap1 knock-out mice had a lower plasma basal insulin level than control mice. Using cultured pancreatic beta-cell lines, INS-1 cells, we confirmed that decreasing Hap1 reduces the number of secreted vesicles and inhibits vesicle exocytosis. Electrophysiology and imaging of intracellular Ca2+ measurements demonstrated that Hap1 depletion significantly reduces the influx of Ca2+ mediated by L-type Ca2+ channels (Cav). This decrease is not due to reduced expression of Cav1.2 channel mRNA but results from the decreased distribution of Cav1.2 on the plasma membrane of INS-1 cells. Fluorescence recovery after photobleaching showed a defective movement of Cav1.2 in Hap1 silencing INS-1 cells. Our findings suggest that Hap1 is important for insulin secretion of pancreatic beta-cells via regulating the intracellular trafficking and plasma membrane localization of Cav1.2, providing new insight into the mechanisms that regulate insulin release from pancreatic beta-cells. |
