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1 Department of Biochemistry, Ghent University Flanders Interuniversity Institute for Biotechnology (VIB09), Gent 9000, Belgium
2 Singapore Institute of Molecular and Cell Biology, Kent Ridge Crescent, Singapore, and Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 2QH, UK
* Present address: Department of Biology, Trinity Western University, 7600 Glover Road, Langley, BC V2Y 1Y1, Canada
Present address: Centre dImmunologie de Marseille-Luminy, CNRS/INSERM/Université de la Méditerranée, Luminy Case 906, 13288 Marseille Cedex 9, France
Present address: Devgen N.V., Technologiepark 9, Blok DF1.60.14, 9052 Zwijnaarde, Belgium
These two authors contributed equally to this work
¶Author for correspondence (e-mail: pujol{at}ciml.univ-mrs.fr)
Accepted 29 April 2002
Cell migration and outgrowth are thought to be based on analogous mechanisms that require repeated cycles of process extension, reading and integration of multiple directional signals, followed by stabilisation in a preferred direction, and renewed extension. We have characterised a C. elegans gene, unc-53, that appears to act cell autonomously in the migration and outgrowth of muscles, axons and excretory canals. Abrogation of unc-53 function disrupts anteroposterior outgrowth in those cells that normally express the gene. Conversely, overexpression of unc-53 in bodywall muscles leads to exaggerated outgrowth. UNC-53 is a novel protein conserved in vertebrates that contains putative SH3- and actin-binding sites. unc-53 interacts genetically with sem-5 and we demonstrated a direct interaction in vitro between UNC-53 and the SH2-SH3 adaptor protein SEM-5/GRB2. Thus, unc-53 is involved in longitudinal navigation and might act by linking extracellular guidance cues to the intracellular cytoskeleton.
Key words: Cell migration, Axonal guidance, Growth cone steering, Cytoskeleton, C. elegans
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