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study identifies a critical role for DOC2B in insulin (show INS Antibodies)-stimulated glucose uptake in adipocytes, and for the synergistic regulation of GSIS by DOC2A (show DOC2A Antibodies) and DOC2B in beta cells.
Data demonstrate that Munc13-1 (show UNC13A Antibodies) and DOC2B have different effects on network activity and that by enhancing asynchronous release, DOC2B exerts its properties to increase spiking activity and elevate synchronization between neurons within network bursts
Hence these data support a working model wherein Doc2b functions as a docking platform/scaffold for transient interactions with the multiple Munc18 isoforms operative in insulin (show INS Antibodies) release, promoting SNARE (show VTI1B Antibodies) assembly.
Doc2b is a limiting factor in SNARE (show VTI1B Antibodies) exocytosis events pertinent to glycaemic regulation in vivo. Doc2b enrichment may provide a novel means to simultaneously boost islet and skeletal muscle function in vivo in the treatment and/or prevention of diabetes.
Mutations that disrupt Ca(2 (show CA2 Antibodies))-binding activity endow Doc2beta with novel functional properties during synaptic transmission.
Doc2b acts to inhibit vesicle priming during prolonged calcium elevations, thus protecting unprimed vesicles from fusing prematurely, and redirecting them to refill the readily releasable pool after relaxation of the calcium signal.
Doc2b is a key positive regulator of Munc18c (show STXBP3 Antibodies)-syntaxin 4 (show STX4 Antibodies)-mediated insulin (show INS Antibodies) secretion as well as of insulin (show INS Antibodies) responsiveness in skeletal muscle, and thus a key effector for glucose homeostasis in vivo.
The data of this study suggested that Doc2s are modulators of spontaneous synaptic transmission that act by a Ca(2 (show CA2 Antibodies)+)-independent mechanism.
study found that Doc2b is a high-affinity Ca2 (show CA2 Antibodies)+ sensor for half (hippocampus) or most (cerebellum) of the spontaneous neurotransmitter release events in CNS synapses
tyrosine phosphorylation of Munc18c (show STXBP3 Antibodies) induces a switch in binding specificity from syntaxin 4 (show STX4 Antibodies) to Doc2beta
Calcium sensor which positively regulates SNARE- dependent fusion of vesicles with membranes. Binds phospholipids in a calcium-dependent manner and may act at the priming stage of fusion by modifying membrane curvature to stimulate fusion. Involved in calcium-triggered exocytosis in chromaffin cells and calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Involved both in glucose-stimulated insulin secretion in pancreatic cells and insulin-dependent GLUT4 transport to the plasma membrane in adipocytes.
, double C2 protein beta
, double C2-like domain-containing protein beta