The microtubule associated protein syntabulin is required for glucose‐stimulated and cAMP‐potentiated insulin secretion

Abstract

Edited by Noboru MizushimaKeywords: Syntabulin Microtubule cAMP Epac2 Insulin secretion INS-1E cell a b s t r a c t Syntabulin is a microtubule-associated protein that mediates anterograde transport of vesicles to neuronal processes. Here, we found that syntabulin was expressed in mouse pancreas and insulin-secreting b-cells, and that it partially co-localized with microtubule and insulin-containing granules. The association of syntabulin with these organelles increased upon glucose stimulation. Knock-down of syntabulin by shRNA reduced both basal and glucose-stimulated insulin secretion, and diminished cAMP-Epac2 and cAMP-PKA potentiated insulin secretion. Additionally, syntabulin was preferentially phosphorylated by the Epac2 agonist 8-pCPT-2 0 -O-Me-cAMP, suggesting that syntabulin could be a novel effector of Epac2 and play a critical role in cAMP-enhanced insulin secretion.

Dynamin Isoforms Decode Action Potential Firing for Synaptic Vesicle Recycling

“…1F), whereas each siRNA significantly reduced individual dynamin isoforms (Fig. 1G) within the standard range for reduction of protein level with siRNA KD (26,27). Importantly, each isoform-specific siRNA did not reduce the expression levels of other dynamin isoforms (Fig.…”

Metastatic triple-negative breast cancer patient with TP53 tumor mutation experienced 11 months progression-free survival on bortezomib monotherapy without adverse events after ending standard treatments with grade 3 adverse events

“…The SYBU mutation also appears to be relevant because its expression is detected in MF, despite being so far known only to be expressed in nerve cells. SYBU encodes syntabulin, which is a microtubule-associated protein that mediates transport of vesicles to neuronal processes (Su et al 2004; Ying et al 2012). TRPM6 is involved in magnesium homeostasis and epithelial magnesium transport, and somatic mutations clustering in the same region have been reported in Chinese breast cancer patients (Zhang et al 2015).…”

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

“…Activation of EPAC2 stimulated the phosphorylation of syntabulin, a microtubule-associated and syntaxin-1-binding protein that attaches syntaxin-containing vesicles to microtubules and kinesin I and mediates anterograde transport of syntaxin-1 to neuronal processes in INS-1E cells (988). Silencing of syntabulin diminished EPAC-potentiated, glucose-stimulated insulin secretion (1166). These studies suggest a potential role of EPAC2's association with the MT cytoskeleton in vesicle trafficking (FIGURE 6).…”