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Dysbindin

Definition:

Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Associates with the BLOC-2 complex to facilitate the transport of TYRP1 independent of AP-3 function. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. Plays a role in the regulation of cell surface exposure of DRD2. May play a role in actin cytoskeleton reorganization and neurite outgrowth. May modulate MAPK8 phosphorylation. Appears to promote neuronal transmission and viability through regulating the expression of SNAP25 and SYN1, modulating PI3-kinase-Akt signaling and influencing glutamatergic release. Regulates the expression of SYN1 through binding to its promoter. Modulates prefrontal cortical activity via the dopamine/D2 pathway.

References:

[1]. Kyoko Kubota, et al. Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal organization. Biochem Biophys Res Commun. 2009 Feb 6;379(2):191-5. [Content Brief]

[2]. Tadahiro Numakawa, et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet. 2004 Nov 1;13(21):2699-708. [Content Brief]

[3]. Santiago M Di Pietro, et al. BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Mol Biol Cell. 2006 Sep;17(9):4027-38. [Content Brief]

[4]. Erkang Fei, et al. Nucleocytoplasmic shuttling of dysbindin-1, a schizophrenia-related protein, regulates synapsin I expression. J Biol Chem. 2010 Dec 3;285(49):38630-40. [Content Brief]

[5]. Subba Rao Gangi Setty, et al. BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles. Mol Biol Cell. 2007 Mar;18(3):768-80. [Content Brief]

[6]. Yukihiko Iizuka, et al. Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization. J Neurosci. 2007 Nov 7;27(45):12390-5. [Content Brief]

[7]. A J Fallgatter, et al. DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in schizophrenic patients--support for the glutamate hypothesis of schizophrenias. Genes Brain Behav. 2010 Jul;9(5):489-97. [Content Brief]

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