Arl2- and Msps-dependent microtubule growth governs asymmetric division

Asymmetric division of neural stem cells is a fundamental strategy to balance their self-renewal and differentiation. It is long thought that microtubules are not essential for cell polarity in asymmetrically dividing Drosophila melanogaster neuroblasts (NBs; neural stem cells). Here, we show that D...

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Published in:	The Journal of cell biology Vol. 212; no. 6; pp. 661 - 676
Main Authors:	Chen, Keng, Koe, Chwee Tat, Xing, Zhanyuan Benny, Tian, Xiaolin, Rossi, Fabrizio, Wang, Cheng, Tang, Quan, Zong, Wenhui, Hong, Wan Jin, Taneja, Reshma, Yu, Fengwei, Gonzalez, Cayetano, Wu, Chunlai, Endow, Sharyn, Wang, Hongyan
Format:	Journal Article
Language:	English
Published:	United States Rockefeller University Press 14-03-2016 The Rockefeller University Press
Subjects:	ADP-Ribosylation Factors - metabolism Animals Binding sites Cell division Cell Division - physiology Cell Polarity - physiology Cells, Cultured Centrosome - metabolism Drosophila melanogaster - metabolism Drosophila melanogaster - physiology Drosophila Proteins - metabolism Insects Membrane Proteins - metabolism Microtubule-Associated Proteins - metabolism Microtubules - metabolism Microtubules - physiology Neural Stem Cells - metabolism Neural Stem Cells - physiology Protein Binding - physiology Stem cells Tubulin - metabolism
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Summary:	Asymmetric division of neural stem cells is a fundamental strategy to balance their self-renewal and differentiation. It is long thought that microtubules are not essential for cell polarity in asymmetrically dividing Drosophila melanogaster neuroblasts (NBs; neural stem cells). Here, we show that Drosophila ADP ribosylation factor like-2 (Arl2) and Msps, a known microtubule-binding protein, control cell polarity and spindle orientation of NBs. Upon arl2 RNA intereference, Arl2-GDP expression, or arl2 deletions, microtubule abnormalities and asymmetric division defects were observed. Conversely, overactivation of Arl2 leads to microtubule overgrowth and depletion of NBs. Arl2 regulates microtubule growth and asymmetric division through localizing Msps to the centrosomes in NBs. Moreover, Arl2 regulates dynein function and in turn centrosomal localization of D-TACC and Msps. Arl2 physically associates with tubulin cofactors C, D, and E. Arl2 functions together with tubulin-binding cofactor D to control microtubule growth, Msps localization, and NB self-renewal. Therefore, Arl2- and Msps-dependent microtubule growth is a new paradigm regulating asymmetric division of neural stem cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9525 1540-8140
DOI:	10.1083/jcb.201503047