Regulation of neurite outgrowth by G(i/o) signaling pathways.
Neurogenesis is a long and winding journey. A neural progenitor cell migrates long distances, differentiates by forming a single axon and multiple dendrites, undergoes maturation, and ultimately survives. The initial formation of neurites during neuronal differentiation, commonly referred to as "neurite outgrowth," can be induced by a large repertoire of signals that stimulate an array of receptors and downstream signaling pathways. The G(i/o) family of heterotrimeric G-proteins are abundantly expressed in the brain and enriched at neuronal growth cones. Recent evidence has uncovered several G(i/o)-coupled receptors that induce neurite outgrowth and has begun to elucidate the underlying molecular mechanisms. Emerging data suggests that signals from several G(i/o)-coupled receptors converge at the transcription factor STAT3 to regulate neurite outgrowth and at Rac1 and Cdc42 to regulate cytoskeletal reorganization. Physiologically, signaling through G(i/o)-coupled cannabinoid receptors is critical for pro percentral nervous system development. As the mechanisms by which G(i/o)-coupled receptors regulate neurite outgrowth are clarified, it is becoming evident that modulating signals from G(i/o) and their receptors has great potential for the treatment of neurodegenerative diseases.
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA. Kenneth.Bromberg@mssm.edu
Kenneth D
KD
Bromberg
Ravi
R
Iyengar
John Cijiang
JC
He
D000818:Animals; D002186:Cannabinoids / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D020439:Growth Cones / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology; D016501:Neurites / Q000502:physiology*; D015398:Signal Transduction
D002186:Cannabinoids; D019206:GTP-Binding Protein alpha Subunits, Gi-Go