title: Mammalian Navigators are microtubule plus-end tracking proteins that can reorganize the cytoskeleton to induce neurite-like extensions.
abstract: Mammalian microtubule plus-end tracking proteins (+TIPs) specifically associate with the ends of growing microtubules. +TIPs are involved in many cellular processes, including mitosis, cell migration and neurite extension. Navigators are mammalian homologues of the C. elegans unc-53 protein, an ATPase that has been linked to the migration and outgrowth of muscles, axons and excretory canals. Here we show that all three mammalian Navigators are +TIPs, consistent with a previous study on Navigator 1 (NAV1) (Martinez-Lopez et al., Mol Cell Neurosci 2005;28:599-612). Overexpression of GFP-tagged Navigators causes displacement of CAP_GLY-motif containing +TIPs, such as CLIP-170, from microtubule ends, suggesting that the Navigator-binding sites on microtubule ends overlap with those of the CAP_GLY-motif proteins. In interphase cells, mammalian Navigators also prominently localize to centrosomes, a localization that does not depend on an intact microtubule network. Fluorescence recovery after photobleaching (FRAP) experiments indicate that NAV1 associates with intracellular structures other than microtubules or centrosomes. Expression of GFP-tagged Navigators induces the formation of neurite-like extensions in non-neuronal cells, showing that Navigators can dominantly alter cytoskeletal behavior. For NAV1 this function depends on its ATPase activity; it is not achieved by a classical type of MT bundling and stabilization. Combined our data suggest that Navigators are +TIPs that can reorganize the cytoskeleton to guide cell shape changes. Our data are consistent with a role for Navigators in neurite outgrowth.
authors.affiliation: Department of Cell Biology and Genetics, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: van Haren
authors.forename: Katharina
authors.initials: K
authors.lastname: Draegestein
authors.forename: Nanda
authors.initials: N
authors.lastname: Keijzer
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Abrahams
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Pieter Johan
authors.initials: PJ
authors.lastname: Peeters
authors.forename: Dieder
authors.initials: D
authors.lastname: Moechars
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008870:Microtubules / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology; D016501:Neurites / Q000648:ultrastructure*; D016900:Neurofilament Proteins / Q000502:physiology; D017434:Protein Structure, Tertiary
chemical_list: D008869:Microtubule-Associated Proteins; C503386:Nav1 protein, mouse; D009363:Neoplasm Proteins; D016900:Neurofilament Proteins; C076744:cytoplasmic linker protein 170; D000251:Adenosine Triphosphatases