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Comments on Kathy D Bueble et al. (2005) International Worm Meeting "A genetic analysis of unc-119 in nervous system development in C.elegans" (0)
Overview
Kathy D Bueble, Helen Chamberlin, & Dave Pilgrim (2005). A genetic analysis of unc-119 in nervous system development in C.elegans presented in International Worm Meeting. Unpublished information; cite only with author permission.
unc-119 encodes a novel protein involved in neural development. Mutants have a variety of neurite defects, including defasciculated nerve fibres and supernumerary axon branches. Research from labs working on the human homologue of UNC-119 shows that UNC-119 interacts with Src kinases and Arl proteins (1,2). Although we have shown that the interaction with Src is likely not biologically relevant in the worm, we do hypothesize that UNC-119 functions in a signal transduction pathway(s) that mediates an axon<sym07>s response to developmental cues. Preliminary genetic data suggests that unc-119 may function redundantly with unc-115, which encodes an actin-binding protein that acts downstream of Rac proteins (3). There are three Rac proteins in C.elegans which have overlapping and redundant function in axon guidance: rac-2, mig-2 and ced-10 (4). unc-115 interacts with the actin cytoskeleton in response to cues from rac-2. Taking into account the role of human UNC-119 as a signaling molecule, we hypothesize that UNC-119 may be acting upstream of the Rac proteins. We are currently constructing unc-119 double mutants with each of the three Rac mutants to determine if UNC-119 is an effector of one or more of the Racs. Interestingly, yeast two-hybrid data from Li et al (5) identified UNC-44 and ARL-3 as positive interactors with UNC-119. We are currently testing if this interaction is biologically relevant in vivo. We are also contructing double mutants with each of these. References: 1- Cen O, et al. J Biol Chem 278: 3847-45. 2- Kobayshi et al, FEBS Lett 543: 26-32. 3- Struckhoff and Lundquist, Development 130: 693-704. 4- Lundquist et al, Development 128: 4475-4488. 5- Li et al, Science 303: 540-543.
Affiliations:
- Ohio State University, Columbus, OH, USA
- Biological Sciences, University of Alberta, Edmonton, AB, Canada