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Impact of Gαz on axon growth and synaptic transmission
Author(s) -
Hultman Rainbo C,
Casey Patrick J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.908.13
Subject(s) - microbiology and biotechnology , neuroscience , rap1 , synaptic vesicle , biology , chemistry , signal transduction , vesicle , biochemistry , membrane
Heterotrimeric G proteins such as Gz play essential roles in cell biology. Gz is differentially expressed in certain brain regions and neuroendocrine cells, and has been shown to couple to endogenous D2 dopamine, 2A adrenergic, and E prostanoid receptors. Furthermore, Gz‐null mice are insensitive to catecholaminergic uptake inhibitor antidepressants. In order to further understand the neurobiology of Gz, its mechanism of action in neurons was characterized. Differential centrifugation was used to separate synaptic membrane components to characterize their Gαz levels. Interestingly, while some Gz was found at the pre‐synaptic plasma membrane, a larger pool of Gz co‐localized with synaptic vesicles. Regulation of synaptic vesicle loading, docking, or release could account for Gz‐null mouse phenotypes, and suggest Gz as a possible target for treatment of monoamine‐related disorders such as schizophrenia, ADHD, and depression. Activated Gz has also been shown to interact with Rap1GAP, a GTPase activating protein for the monomeric G‐protein Rap1. Brain‐derived neurotrophin factor (BDNF), an important regulator of normal neuron growth, signals through Rap1. We show that BDNF‐stimulated axon growth in cortical neurons is inhibited by constitutively active Gαz, suggesting Gz as an intriguing target for further study. This work was supported by Grant GM55717 from the National Institutes of Health