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Here the authors report that analogous ring-like oligomers assemble from the C2AB domains of other Syt (show SS18 Proteins) isoforms (Syt2 (show SYT2 Proteins), Syt7 (show SYT7 Proteins), Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts).
promoter hypermethylation and silencing of the DOC2B gene is an early and frequent event during cervical carcinogenesis and whose reduced expression due to DNA promoter methylation may lead to selective cervical tumor growth
Study analyzed Doc2alpha and Doc2beta and found that Doc2 (show DAB2 Proteins) responds to changes in [Ca2 (show CA2 Proteins)+], with markedly slower kinetics as compared to the cytosolic domain of syt I (syt (show SYT1 Proteins)), and operates on a timescale consistent with asynchronous neurotransmitter release.
study identifies a critical role for DOC2B in insulin (show INS Proteins)-stimulated glucose uptake in adipocytes, and for the synergistic regulation of GSIS by DOC2A (show DOC2A Proteins) and DOC2B in beta cells.
Data demonstrate that Munc13-1 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 Proteins) release, promoting SNARE (show VTI1B Proteins) assembly.
Doc2b is a limiting factor in SNARE (show VTI1B Proteins) 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 Proteins))-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 Proteins)-syntaxin 4 (show STX4 Proteins)-mediated insulin (show INS Proteins) secretion as well as of insulin (show INS Proteins) 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 Proteins)+)-independent mechanism.
study found that Doc2b is a high-affinity Ca2 (show CA2 Proteins)+ sensor for half (hippocampus) or most (cerebellum) of the spontaneous neurotransmitter release events in CNS synapses
tyrosine phosphorylation of Munc18c (show STXBP3 Proteins) induces a switch in binding specificity from syntaxin 4 (show STX4 Proteins) to Doc2beta
There are at least two protein isoforms of the Double C2 protein, namely alpha (DOC2A) and beta (DOC2B), which contain two C2-like domains. DOC2A and DOC2B are encoded by different genes\; these genes are at times confused with the unrelated DAB2 gene which was initially named DOC-2. DOC2B is expressed ubiquitously and is suggested to be involved in Ca(2+)-dependent intracellular vesicle trafficking in various types of cells.
double C2-like domains, beta-like
, double C2-like domains, beta
, double C2-like domain-containing protein beta-like
, double C2, beta
, double C2-like domain-containing protein beta
, double C2 protein beta