Neuronal cell shape and neurite initiation are regulated by the Ndr kinaseSAX-1, a member of the Orb6/COT-1/Warts serine/threonine kinase family

The Caenorhabditis elegans sax-1 gene regulates several aspects of neuronal cell shape. sax-1 mutants have expanded cell bodies and Ectopic neurites i n many classes of neurons, suggesting that SAX-1 functions to restrict cell and neurite growth. The ectopic neurites in sensory neurons of sax-1 mutan ts resemble the defects caused by decreased sensory activity. However, the activity-dependent pathway, mediated in part by the UNC-43 calcium/calmodul in-dependent kinase II, functions in parallel with SAX-1 to suppress neurit e initiation, sax-1 encodes a serine/threonine kinase in the Ndr family tha t is related to the Orb6 (Schizosaccharomyces pombe), Warts/Lats (Drosophil a), and COT-1 (Neurospora) kinases that function in cell shape regulation. These kinases have similarity to Rho kinases but lack consensus Rho-binding domains. Dominant negative mutations in the C. elegans RhoA GTPase cause n euronal cell shape defects similar to those of sax-1 mutants, and genetic i nteractions between rhoA and sax-1 suggest shared functions. These results suggest that SAX-1/Ndr kinases are endogenous inhibitors of neurite initiat ion and cell spreading.