Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons

Wen Shin Chen, Yi Ju Chen, Yung An Huang, Bing Yuan Hsieh, Ho Chieh Chiu, Pei Ying Kao, Chih Yuan Chao, Eric Hwang*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish
Article number42297
JournalScientific reports
Volume7
DOIs
StatePublished - 13 Feb 2017

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    Chen, W. S., Chen, Y. J., Huang, Y. A., Hsieh, B. Y., Chiu, H. C., Kao, P. Y., Chao, C. Y., & Hwang, E. (2017). Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons. Scientific reports, 7, [42297]. https://doi.org/10.1038/srep42297