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Publication
Synaptotagmin 4 Regulates Pancreatic ß Cell Maturation by Modulating the Ca2+
Sensitivity of Insulin Secretion Vesicles.
Authors Huang C, Walker EM, Dadi PK, Hu R, Xu Y, Zhang W, Sanavia T, Mun J, Liu J, Nair
GG, Tan HYA, Wang S, Magnuson MA, Stoeckert CJ, Hebrok M, Gannon M, Han W, Stein
R, Jacobson DA, Gu G
Submitted By Submitted Externally on 5/25/2018
Status Published
Journal Developmental cell
Year 2018
Date Published 5/1/2018
Volume : Pages 45 : 347 - 361.e5
PubMed Reference 29656931
Abstract Islet ß cells from newborn mammals exhibit high basal insulin secretion and poor
glucose-stimulated insulin secretion (GSIS). Here we show that ß cells of
newborns secrete more insulin than adults in response to similar intracellular
Ca2+ concentrations, suggesting differences in the Ca2+ sensitivity of insulin
secretion. Synaptotagmin 4 (Syt4), a non-Ca2+ binding paralog of the ß cell Ca2+
sensor Syt7, increased by ~8-fold during ß 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-ßH1 cells, a human ß
cell line. These findings reveal the role that altered Ca2+ sensing plays in
regulating ß cell maturation.




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