title: Calsyntenin 1-mediated trafficking of axon guidance receptors regulates the switch in axonal responsiveness at a choice point.
abstract: Axon guidance at choice points depends on the precise regulation of guidance receptors on the growth cone surface. Upon arrival at the intermediate target or choice point, a switch from attraction to repulsion is required for the axon to move on. Dorsal commissural (dI1) axons crossing the ventral midline of the spinal cord in the floor plate represent a convenient model for the analysis of the molecular mechanism underlying the switch in axonal behavior. We identified in chick a role for calsyntenin 1 in the regulation of vesicular trafficking of guidance receptors in dI1 axons at choice points. In cooperation with RabGDI, calsyntenin 1 shuttles Rab11-positive vesicles containing Robo1 to the growth cone surface in a precisely regulated manner. By contrast, calsyntenin 1-mediated trafficking of frizzled 3, a guidance receptor in the Wnt pathway, is independent of RabGDI. Thus, tightly regulated insertion of guidance receptors, which is required for midline crossing and the subsequent turn into the longitudinal axis, is achieved by specific trafficking.
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland.
authors.forename: Tobias A
authors.initials: TA
authors.lastname: Alther
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland.
authors.forename: Elena
authors.initials: E
authors.lastname: Domanitskaya
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland esther.stoeckli@imls.uzh.ch.
authors.forename: Esther T
authors.initials: ET
authors.lastname: Stoeckli
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002645:Chickens; D002522:Chlorocebus aethiops; D020868:Gene Silencing; D020439:Growth Cones / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D030161:Avian Proteins; D002135:Calcium-Binding Proteins; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D011956:Receptors, Cell Surface
keywords: Chicken; Commissural axon guidance; Frizzled 3; GDI1; Midline crossing; RabGDI; Robo1; Wnt signaling