title: Gαz regulates BDNF-induction of axon growth in cortical neurons.
abstract: The disruption of neurotransmitter and neurotrophic factor signaling in the central nervous system (CNS) is implicated as the root cause of neuropsychiatric disorders, including schizophrenia, epilepsy, chronic pain, and depression. Therefore, identifying the underlying molecular mechanisms by which neurotransmitter and neurotrophic factor signaling regulates neuronal survival or growth may facilitate identification of more effective therapies for these disorders. Previously, our lab found that the heterotrimeric G protein, Gz, mediates crosstalk between G protein-coupled receptors and neurotrophin signaling in the neural cell line PC12. These data, combined with Gαz expression profiles--predominantly in neuronal cells with higher expression levels corresponding to developmental times of target tissue innervation--suggested that Gαz may play an important role in neurotrophin signaling and neuronal development. Here, we provide evidence in cortical neurons, both manipulated ex vivo and those cultured from Gz knockout mice, that Gαz is localized to axonal growth cones and plays a significant role in the development of axons of cortical neurons in the CNS. Our findings indicate that Gαz inhibits BDNF-stimulated axon growth in cortical neurons, establishing an endogenous role for Gαz in regulating neurotrophin signaling in the CNS.
authors: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA; Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 169857, Republic of Singapore.
authors: Rainbo
authors: R
authors: Hultman
authors: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 169857, Republic of Singapore.
authors: Udhaya
authors: U
authors: Kumari
authors: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
authors: Nadine
authors: N
authors: Michel
authors: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA; Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 169857, Republic of Singapore. Electronic address: casey006@mc.duke.edu.
authors: Patrick J
authors: PJ
authors: Casey
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D048708:Cell Growth Processes; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D044385:GTP-Binding Protein alpha Subunits; C490964:Gnaz protein, mouse
keywords: BDNF; G proteins; GNAZ; Neurotrophin