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Gαz regulates BDNF-induction of axon growth in cortical neurons
Journal article   Peer reviewed

Gαz regulates BDNF-induction of axon growth in cortical neurons

Rainbo Hultman, Udhaya Kumari, Nadine Michel and Patrick J Casey
Molecular and cellular neurosciences, Vol.58, pp.53-61
01/2014
DOI: 10.1016/j.mcn.2013.12.004
PMCID: PMC4096435
PMID: 24321455
url
http://doi.org/10.1016/j.mcn.2013.12.004View
Open Access

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.
Neurotrophin GNAZ G proteins BDNF

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