title: Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons.
abstract: The microtubule (MT) cytoskeleton is essential for the formation of morphologically appropriate neurons. The existence of the acentrosomal MT organizing center in neurons has been proposed but its identity remained elusive. Here we provide evidence showing that TPX2 is an important component of this acentrosomal MT organizing center. First, neurite elongation is compromised in TPX2-depleted neurons. In addition, TPX2 localizes to the centrosome and along the neurite shaft bound to MTs. Depleting TPX2 decreases MT formation frequency specifically at the tip and the base of the neurite, and these correlate precisely with the regions where active GTP-bound Ran proteins are enriched. Furthermore, overexpressing the downstream effector of Ran, importin, compromises MT formation and neuronal morphogenesis. Finally, applying a Ran-importin signaling interfering compound phenocopies the effect of TPX2 depletion on MT dynamics. Together, these data suggest a model in which Ran-dependent TPX2 activation promotes acentrosomal MT nucleation in neurons.
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.|Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.|Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Wen-Shin
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.|Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Yung-An
authors.initials: YA
authors.lastname: Huang
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Bing-Yuan
authors.initials: BY
authors.lastname: Hsieh
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Ho-Chieh
authors.initials: HC
authors.lastname: Chiu
authors.affiliation: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Kao
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Chao
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.|Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.|Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, Taiwan.|Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Eric
authors.initials: E
authors.lastname: Hwang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology; D028901:alpha Karyopherins / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011799:Quinazolines; C572046:TPX2 protein, mouse; D028901:alpha Karyopherins; D028961:beta Karyopherins; C568452:importazole; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein