| First Author | Huang C | Year | 2018 |
| Journal | Dev Cell | Volume | 45 |
| Issue | 3 | Pages | 347-361.e5 |
| PubMed ID | 29656931 | Mgi Jnum | J:263864 |
| Mgi Id | MGI:6191854 | Doi | 10.1016/j.devcel.2018.03.013 |
| Citation | Huang C, et al. (2018) Synaptotagmin 4 Regulates Pancreatic beta Cell Maturation by Modulating the Ca(2+) Sensitivity of Insulin Secretion Vesicles. Dev Cell 45(3):347-361.e5 |
| abstractText | Islet beta cells from newborn mammals exhibit high basal insulin secretion and poor glucose-stimulated insulin secretion (GSIS). Here we show that beta cells of newborns secrete more insulin than adults in response to similar intracellular Ca(2+) concentrations, suggesting differences in the Ca(2+) sensitivity of insulin secretion. Synaptotagmin 4 (Syt4), a non-Ca(2+) binding paralog of the beta cell Ca(2+) sensor Syt7, increased by approximately 8-fold during beta cell maturation. Syt4 ablation increased basal insulin secretion and compromised GSIS. Precocious Syt4 expression repressed basal insulin secretion but also impaired islet morphogenesis and GSIS. Syt4 was localized on insulin granules and Syt4 levels inversely related to the number of readily releasable vesicles. Thus, transcriptional regulation of Syt4 affects insulin secretion; Syt4 expression is regulated in part by Myt transcription factors, which repress Syt4 transcription. Finally, human SYT4 regulated GSIS in EndoC-betaH1 cells, a human beta cell line. These findings reveal the role that altered Ca(2+) sensing plays in regulating beta cell maturation. |
