The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans

G3: Genes, Genomes, Genetics

article

Jamie K. Alan¹  Sara K. Robinson²  Katie L. Magsig²  Rafael S. Demarco³  Erik A. Lundquist³ 

[1] Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824;College of Medicine, Central Michigan University, Mount Pleasant, MI 48859;Department of Molecular Biosciences, University of Kansas, Lawrence, KS 60045

关键词: CHW-1;    SAX-3/Robo;    axon pathfinding;    CRP-1;    CDC-42;   

DOI  :  10.1534/g3.118.200148

学科分类：社会科学、人文和艺术（综合）

来源: Genetics Society of America

【 摘 要 】

During development, neuronal cells extend an axon toward their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the Caenorhabditis elegans ( C. elegans ) atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. chw-1 (Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance. Furthermore, proper levels of chw-1 expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1 ) alter axon guidance and neural migration. Additionally, we showed that chw-1 genetically interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases chw-1 and crp-1 in axon guidance. Furthermore, this is the first evidence of genetic interaction between chw-1 and the guidance receptor sax-3 . These data suggest that chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.

【 授权许可】

CC BY|CC BY-NC