title: Cytoplasmic linker proteins regulate neuronal polarization through microtubule and growth cone dynamics.
abstract: Axon formation is a hallmark of initial neuronal polarization. This process is thought to be regulated by enhanced microtubule stability in the subsequent axon and changes in actin dynamics in the future axonal growth cone. Here, we show that the microtubule end-binding proteins cytoplasmic linker protein (CLIP)-115 and CLIP-170 were enriched in the axonal growth cone and extended into the actin-rich domain of the growth cone. CLIPs were necessary for axon formation and sufficient to induce an axon. The regulation of axonal microtubule stabilization by CLIPs enabled the protrusion of microtubules into the leading edge of the axonal growth cone. Moreover, CLIPs positively regulated growth cone dynamics and restrained actin arc formation, which was necessary for axon growth. In fact, in neurons without CLIP activity, axon formation was restored by actin destabilization or myosin II inhibition. Together, our data suggest that CLIPs enable neuronal polarization by controlling the stabilization of microtubules and growth cone dynamics.
authors.affiliation: Max Planck Institute of Neurobiology, Junior Research Group Axonal Growth and Regeneration, 82152 Martinsried, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Neukirchen
authors.forename: Frank
authors.initials: F
authors.lastname: Bradke
mesh_terms: D000199:Actins / Q000502:physiology / Q000648:ultrastructure; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D020439:Growth Cones / Q000502:physiology* / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008870:Microtubules / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D051381:Rats
chemical_list: D000199:Actins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C109878:cytoplasmic linker protein 115; C076744:cytoplasmic linker protein 170