title: Calsyntenin-1 regulates axon branching and endosomal trafficking during sensory neuron development in vivo.
abstract: Precise regulation of axon branching is crucial for neuronal circuit formation, yet the mechanisms that control branch formation are not well understood. Moreover, the highly complex morphology of neurons makes them critically dependent on protein/membrane trafficking and transport systems, although the functions for membrane trafficking in neuronal morphogenesis are largely undefined. Here we identify a kinesin adaptor, Calsyntenin-1 (Clstn-1), as an essential regulator of axon branching and neuronal compartmentalization in vivo. We use morpholino knockdown and a Clstn-1 mutant to show that Clstn-1 is required for formation of peripheral but not central sensory axons, and for peripheral axon branching in zebrafish. We used live imaging of endosomal trafficking in vivo to show that Clstn-1 regulates transport of Rab5-containing endosomes from the cell body to specific locations of developing axons. Our results suggest a model in which Clstn-1 patterns separate axonal compartments and define their ability to branch by directing trafficking of specific endosomes.
authors.affiliation: Department of Zoology, Department of Neuroscience, Neuroscience Training Program, Medical Scientist Training Program, and.
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Ponomareva
authors.affiliation: Department of Zoology, Department of Neuroscience.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Holmen
authors.affiliation: Department of Zoology, Department of Neuroscience.
authors.forename: Aiden J
authors.initials: AJ
authors.lastname: Sperry
authors.affiliation: Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Eliceiri
authors.affiliation: Department of Zoology, Department of Neuroscience, Neuroscience Training Program, Medical Scientist Training Program, and mchalloran@wisc.edu.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Halloran
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D011992:Endosomes / Q000502:physiology* / Q000648:ultrastructure; D023421:Models, Animal; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology* / Q000648:ultrastructure*; D015027:Zebrafish
chemical_list: C503225:CLSTN1 protein, human; D002135:Calcium-Binding Proteins
keywords: axon branching; calsyntenin; endosome; polarity; trafficking; zebrafish