Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Regulation of neurite outgrowth by Gi/o signaling pathways
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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 Gi/o family of heterotrimeric G-proteins are abundantly expressed in the brain and enriched at neuronal growth cones. Recent evidence has uncovered several Gi/o-coupled receptors that induce neurite outgrowth and has begun to elucidate the underlying molecular mechanisms. Emerging data suggests that signals from several Gi/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 Gi/o-coupled cannabinoid receptors is critical for proper central nervous system development. As the mechanisms by which Gi/o-coupled receptors regulate neurite outgrowth are clarified, it is becoming evident that modulating signals from Gi/o and their receptors has great potential for the treatment of neurodegenerative diseases.