Neuronal cell shape and neurite initiation are regulated by the Ndr kinase SAX-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 in many classes of neurons, suggesting that SAX-1 functions to restrict cell and neurite growth. The ectopic neurites in sensory neurons of sax-1 mutants resemble the defects caused by decreased sensory activity. However, the activity-dependent pathway, mediated in part by the UNC-43 calcium/calmodulin-dependent kinase II, functions in parallel with SAX-1 to suppress neurite initiation. sax-1 encodes a serine/threonine kinase in the Ndr family that is related to the Orb6 (Schizosaccharomyces pombe), Warts/Lats (Drosophila), 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 neuronal cell shape defects similar to those of sax-1 mutants, and genetic interactions between rhoA and sax-1 suggest shared functions. These results suggest that SAX-1/Ndr kinases are endogenous inhibitors of neurite initiation and cell spreading.
Zallen
J A
JA
Howard Hughes Medical Institute, Programs in Developmental Biology, Neuroscience, and Genetics, Department of Anatomy and Department of Biochemistry and Biophysics, The University of California, San Francisco, California 94143, USA.
Peckol
E L
EL
Tobin
D M
DM
Bargmann
C I
CI
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D048429:Cell Size; D004330:Drosophila / Q000235:genetics; D005091:Exons; D017353:Gene Deletion; D049452:Green Fluorescent Proteins; D007438:Introns; D008164:Luminescent Proteins / Q000032:analysis; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009491:Neurospora / Q000235:genetics; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C415970:sax-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases