UNC-71, a disintegrin and metalloprotease (ADAM) protein, regulates motor axon guidance and sex myoblast migration in C. elegans.
The migration of cells and growth cones is a process that is guided by extracellular cues and requires the controlled remodeling of the extracellular matrix along the migratory path. The ADAM proteins are important regulators of cellular adhesion and recognition because they can combine regulated proteolysis with modulation of cell adhesion. We report that the C. elegans gene unc-71 encodes a unique ADAM with an inactive metalloprotease domain. Loss-of-function mutations in unc-71 cause distinct defects in motor axon guidance and sex myoblast migration. Many unc-71 mutations affect the disintegrin and the cysteine-rich domains, supporting a major function of unc-71 in cell adhesion. UNC-71 appears to be expressed in a selected set of cells. Genetic mosaic analysis and tissue-specific expression studies indicate that unc-71 acts in a cell non-autonomous manner for both motor axon guidance and sex myoblast migration. Finally, double mutant analysis of unc-71 with other axon guidance signaling molecules suggests that UNC-71 probably functions in a combinatorial manner with integrins and UNC-6/netrin to provide distinct axon guidance cues at specific choice points for motoneurons.
Huang
Xun
X
Department of Molecular, Cellular and Developmental Biology, Sinsheimer Laboratories, University of California, Santa Cruz, CA 95064, USA.
Huang
Peng
P
Robinson
Matthew K
MK
Stern
Michael J
MJ
Jin
Yishi
Y
D000483:Alleles; D000818:Animals; D001369:Axons; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D003001:Cloning, Molecular; D003545:Cysteine / Q000737:chemistry; D049452:Green Fluorescent Proteins; D016023:Integrins / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008957:Models, Genetic; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation; D032446:Myoblasts / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D010641:Phenotype; D017434:Protein Structure, Tertiary; D014018:Tissue Distribution; D019076:Transgenes; D025521:Tumor Suppressor Proteins
D029742:Caenorhabditis elegans Proteins; D016023:Integrins; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D000075388:Netrin-1; C104620:UNC-71 protein, C elegans; D008666:Metalloendopeptidases; D003545:Cysteine