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The Journal of Neuroscience, February 1, 2000, 20(3):1096-1108

short stop Is Allelic to kakapo, and Encodes Rod-Like Cytoskeletal-Associated Proteins Required for Axon Extension

Seungbok Lee1, Kerri-Lee Harris2, Paul M. Whitington2, and Peter A. Kolodziej1

1 Department of Cell Biology, Center for Molecular Neuroscience and Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232-0295, and 2 Molecular and Cellular Biology, School of Biological Sciences, University of New England, Armidale, New South Wales, Australia 2351

short stop (shot) is required for sensory and motor axons to reach their targets in the Drosophila embryo. Growth cones in shot mutants initiate at the normal times, and they appear normal with respect to overall morphology and their abilities to orient and fasciculate. However, sensory axons are unable to extend beyond a short distance from the cell body, and motor axons are unable to reach target muscles. The shot gene encodes novel actin binding proteins that are related to plakins and dystrophin and expressed in axons during development. The longer isoforms identified are predicted to contain an N-terminal actin binding domain, a long central triple helical coiled-coil domain, and a C-terminal domain that contains two EF-hand Ca2+ binding motifs and a short stretch of homology to the growth arrest-specific 2 protein. Other isoforms lack all or part of the actin binding domains or are truncated and contain a different C-terminal domain. Only the isoforms containing full-length actin binding domains are detectably expressed in the nervous system. shot is allelic to kakapo, a gene that may function in integrin-mediated adhesion in the wing and embryo. We propose that Shot's interactions with the actin cytoskeleton allow sensory and motor axons to extend.

Key words: Drosophila; cytoskeleton; GAS2; axon; growth cone; short stop; kakapo


Copyright © 2000 Society for Neuroscience  0270-6474/00/2031096-13$05.00/0


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