SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells.

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.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}