MAX-1, a novel PH/MyTH4/FERM domain cytoplasmic protein implicated in netrin-mediated axon repulsion.
The netrin UNC-6 repels motor axons by activating the UNC-5 receptor alone or in combination with the UNC-40/DCC receptor. In a genetic screen for C. elegans mutants exhibiting partial defects in motor axon projections, we isolated the max-1 gene (required for motor neuron axon guidance). max-1 loss-of-function mutations cause fully penetrant but variable axon guidance defects. Mutations in unc-5 and unc-6, but not in unc-40, dominantly enhance the mutant phenotypes of max-1, whereas overexpression of unc-5 or unc-6, but not of unc-40, bypasses the requirement for max-1. MAX-1 proteins contain PH, MyTH4, and FERM domains and appear to be localized to neuronal processes. Human MAX-1 and UNC5H2 colocalize in discrete subcellular regions of transfected cells. Our results suggest a possible role for MAX-1 in netrin-induced axon repulsion by modulating the UNC-5 receptor signaling pathway.
Huang
Xun
X
Department of Molecular, Cellular, and Developmental Biology, Santa Cruz, CA 95064, USA.
Cheng
Hwai Jong
HJ
Tessier-Lavigne
Marc
M
Jin
Yishi
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002874:Chromosome Mapping; D003593:Cytoplasm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D000075386:Netrin Receptors; D000075388:Netrin-1; D000075385:Netrins; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D017434:Protein Structure, Tertiary / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D015801:Helminth Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D000075385:Netrins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D025521:Tumor Suppressor Proteins; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans; C459680:max-1 protein, C elegans; C077588:UNC-5 protein, C elegans; D000075388:Netrin-1