The tripartite motif protein MADD-2 functions with the receptor UNC-40 (DCC) in Netrin-mediated axon attraction and branching.
Neurons innervate multiple targets by sprouting axon branches from a primary axon shaft. We show here that the ventral guidance factor unc-6 (Netrin), its receptor unc-40 (DCC), and the gene madd-2 stimulate ventral axon branching in C. elegans chemosensory and mechanosensory neurons. madd-2 also promotes attractive axon guidance to UNC-6 and assists unc-6- and unc-40-dependent ventral recruitment of the actin regulator MIG-10 in nascent axons. MADD-2 is a tripartite motif protein related to MID-1, the causative gene for the human developmental disorder Opitz syndrome. MADD-2 and UNC-40 proteins preferentially localize to a ventral axon branch that requires their function; genetic results indicate that MADD-2 potentiates UNC-40 activity. Our results identify MADD-2 as an UNC-40 cofactor in axon attraction and branching, paralleling the role of UNC-5 in repulsion, and provide evidence that targeting of a guidance factor to specific axonal branches can confer differential responsiveness to guidance cues.
Hao
Joe C
JC
Howard Hughes Medical Institute, Department of Anatomy, Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA.
Adler
Carolyn E
CE
Mebane
Leslie
L
Gertler
Frank B
FB
Bargmann
Cornelia I
CI
Tessier-Lavigne
Marc
M
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D003463:Cues; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D000075385:Netrins; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075385:Netrins; D009687:Nuclear Proteins; C551653:TRIM-9 protein, C elegans; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans; C469337:Trim9 protein, mouse; D044767:Ubiquitin-Protein Ligases