Rho family GTPases in neuronal differentiation, development, survival, and death

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Background

Rho GTPases are a family of molecular switches that critically mediate many cellular processes such as proliferation, survival, and death. The most well described members of the Rho GTPase family are RhoA, Rac1, and Cdc42 which are each known to regulate actin cytoskeletal dynamics. Thus, it is not surprising that Rho GTPases play a crucial function in neuronal growth cone dynamics and dendritic spine morphogenesis. Specifically, Rac1 and Cdc42 generally induce neurite outgrowth and dendritic spine morphogenesis, while RhoA typically stimulates neurite retraction. In addition to regulating neuronal cytoskeletal dynamics, previous work has demonstrated a critical function for Rho GTPase family members in neuronal development and survival. Indeed, dysregulation of Rho GTPase family members has been implicated in several disorders of the central nervous system including, Down Syndrome, Fragile X Mental Retardation Syndrome, Amyotrophic Lateral Sclerosis, amongst many others. In addition to typical Rho GTPase family members that significantly mediate cytoskeleton dynamics and survival in neurons, more recent data highlight atypical Mitochondrial Rho-like GTPases (Miro1 and Miro2, in humans) as important components of the adaptor complex that tethers mitochondria to kinesin motors, thereby inducing directed transport of mitochondria throughout cellular bodies and processes. Thus, dysregulation of Miro GTPases has been underscored as a potential causative factor in neurodegenerative diseases characterized by defects in mitochondrial transport such as Marie-Charcot-Tooth Syndrome and Parkinson’s disease. Given the essential neuronal functions of both typical Rho GTPases and atypical Rho-like GTPases, this abstract is a call for manuscripts examining the function of either Rho GTPase or Rho-like GTPase family members in a variety of neuronal models (in vitro cell culture models, in vivo animal models, etc.). Appropriate papers include either discussions of new data or reviews of current literature examining the involvement of Rho GTPases or Rho-like GTPases in neuronal differentiation, development, survival, and death.

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