SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells.
Sci Rep
; 7(1): 248, 2017 03 21.
Article
em En
| MEDLINE
| ID: mdl-28325894
ABSTRACT
Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca2+. Here we show that tomosyn, which suppresses insulin exocytosis by binding syntaxin1A, does so in a manner which requires its SUMOylation. Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca2+-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca2+-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca2+ influx. Together our results suggest that tomosyn acts as a key signaling hub in insulin secretion by integrating signals mediated by metabolism-dependent de-SUMOylation and electrically-induced entry of Ca2+ to regulate the availability of exocytotic proteins required for the amplification of insulin secretion.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Células Secretoras de Insulina
/
Sintaxina 1
/
Proteínas R-SNARE
/
Sumoilação
/
Secretagoginas
/
Insulina
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá