Axon guidance receptors modulate the growth cone cytoskeleton through signaling pathways that are not well understood. Here, we describe the C. elegans unc-115 gene, which encodes a candidate cytoskeletal linker protein that acts in axon guidance. unc-115 mutants have defects in a subset of axons, particularly as the affected axons change environments during outgrowth. The unc-115 gene encodes a putative actin-binding protein that is similar to the human actin-binding protein abLIM/limatin; it has a villin headpiece domain and three LIM domains that could mediate protein interactions. unc-115 is expressed in neurons during their development and is required cell-autonomously in certain neurons for normal axon guidance. We propose that UNC-115 modulates the growth cone actin cytoskeleton in response to signals received by growth cone receptors.
Bibliographical noteFunding Information:
We thank Shannon Grantner and Liqin Tong for excellent technical assistance, Andrew Fire, Noelle L’Etoile, and Joe Chou for providing unpublished clones, Jen Zallen for helpful observations, Tim Yu for confocal assistance, and Sue Kirch, Erin Peckol and Jen Zallen for comments on the manuscript. Some nematode strains used in this work were provided by the Caenorhabditis elegans Genetics Center. The work was supported by the Howard Hughes Medical Institute and by National Institutes of Health grants GM22387 (to R. K. H.) and HD22163 (to J. E. S.). E. A. L. was supported by the Howard Hughes Medical Institute and a Damon Runyon–Walter Winchell Cancer Research Fund fellowship. C. I. B. is an Assistant Investigator of the Howard Hughes Medical Institute.