title: UNC-33 (CRMP) and ankyrin organize microtubules and localize kinesin to polarize axon-dendrite sorting.
abstract: The polarized distribution of neuronal proteins to axons and dendrites relies on microtubule-binding proteins such as CRMP, directed motors such as the kinesin UNC-104 (Kif1A) and diffusion barriers such as ankyrin. The causative relationships among these molecules are unknown. We show here that Caenorhabditis elegans CRMP (UNC-33) acts early in neuronal development, together with ankyrin (UNC-44), to organize microtubule asymmetry and axon-dendrite sorting. In unc-33 and unc-44 mutants, axonal proteins were mislocalized to dendrites and vice versa, suggesting bidirectional failures of axon-dendrite identity. unc-44 directed UNC-33 localization to axons, where it was enriched in a region that resembled the axon initial segment. unc-33 and unc-44 were both required to establish the asymmetric dynamics of axonal and dendritic microtubules; in their absence, microtubules were disorganized, the axonal kinesin UNC-104 invaded dendrites, and inappropriate UNC-104 activity randomized axonal protein sorting. We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.
authors.affiliation: Laboratory of Neural Circuits and Behavior, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA.
authors.forename: Tapan A
authors.initials: TA
authors.lastname: Maniar
authors.forename: Miriam
authors.initials: M
authors.lastname: Kaplan
authors.forename: George J
authors.initials: GJ
authors.lastname: Wang
authors.forename: Kang
authors.initials: K
authors.lastname: Shen
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Jocelyn E
authors.initials: JE
authors.lastname: Shaw
authors.forename: Sandhya P
authors.initials: SP
authors.lastname: Koushika
authors.forename: Cornelia I
authors.initials: CI
authors.lastname: Bargmann
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D017487:Ankyrins; D029742:Caenorhabditis elegans Proteins; D009414:Nerve Growth Factors; C078652:unc-33 protein, C elegans; D016547:Kinesins
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