title: Arl2- and Msps-dependent microtubule growth governs asymmetric division.
abstract: 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.
authors.affiliation: Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore 169857 National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456.
authors.forename: Keng
authors.initials: K
authors.lastname: Chen
authors.affiliation: Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore 169857 National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456.
authors.forename: Chwee Tat
authors.initials: CT
authors.lastname: Koe
authors.affiliation: Department of Cell Biology, Duke University, Duke University Medical Center, Durham, NC 27710.
authors.forename: Zhanyuan Benny
authors.initials: ZB
authors.lastname: Xing
authors.affiliation: Neuroscience Center of Excellence, Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, LA 70112.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Institute for Research in Biomedicine Barcelona, 08028 Barcelona, Spain.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore 169857.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604 Department of Biological Sciences, National University of Singapore, Singapore 117604.
authors.forename: Quan
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604 Department of Biological Sciences, National University of Singapore, Singapore 117604.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zong
authors.affiliation: Institute of Molecular and Cell Biology, Singapore 138673.
authors.forename: Wan Jin
authors.initials: WJ
authors.lastname: Hong
authors.affiliation: National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
authors.forename: Reshma
authors.initials: R
authors.lastname: Taneja
authors.affiliation: Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore 169857 National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456 Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604 Department of Biological Sciences, National University of Singapore, Singapore 117604.
authors.forename: Fengwei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Institute for Research in Biomedicine Barcelona, 08028 Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.
authors.forename: Cayetano
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: Neuroscience Center of Excellence, Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, LA 70112.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Wu
authors.affiliation: Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore 169857 Department of Cell Biology, Duke University, Duke University Medical Center, Durham, NC 27710.
authors.forename: Sharyn
authors.initials: S
authors.lastname: Endow
authors.affiliation: Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore 169857 National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597 hongyan.wang@duke-nus.edu.sg.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism* / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000502:physiology; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D014404:Tubulin / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D014404:Tubulin; C121511:msps protein, Drosophila; C097313:ADP-ribosylation factor related proteins; D020727:ADP-Ribosylation Factors