title: An ana2/ctp/mud complex regulates spindle orientation in Drosophila neuroblasts.
abstract: Drosophila neural stem cells, larval brain neuroblasts (NBs), align their mitotic spindles along the apical/basal axis during asymmetric cell division (ACD) to maintain the balance of self-renewal and differentiation. Here, we identified a protein complex composed of the tumor suppressor anastral spindle 2 (Ana2), a dynein light-chain protein Cut up (Ctp), and Mushroom body defect (Mud), which regulates mitotic spindle orientation. We isolated two ana2 alleles that displayed spindle misorientation and NB overgrowth phenotypes in larval brains. The centriolar protein Ana2 anchors Ctp to centrioles during ACD. The centriolar localization of Ctp is important for spindle orientation. Ana2 and Ctp localize Mud to the centrosomes and cell cortex and facilitate/maintain the association of Mud with Pins at the apical cortex. Our findings reveal that the centrosomal proteins Ana2 and Ctp regulate Mud function to orient the mitotic spindle during NB asymmetric division.
authors.affiliation: Neuroscience & Behavioral Disorder Program, Duke-National University of Singapore Graduate Medical School Singapore, Singapore, Singapore.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Jens
authors.initials: J
authors.lastname: Januschke
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Rossi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Izumi
authors.forename: Gisela
authors.initials: G
authors.lastname: Garcia-Alvarez
authors.forename: Serene Sze Ling
authors.initials: SS
authors.lastname: Gwee
authors.forename: Swee Beng
authors.initials: SB
authors.lastname: Soon
authors.forename: Harpreet Kaur
authors.initials: HK
authors.lastname: Sidhu
authors.forename: Fengwei
authors.initials: F
authors.lastname: Yu
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzaki
authors.forename: Cayetano
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division; D002502:Centrioles / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C547835:Ana2 protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D008565:Membrane Proteins; C411670:Mud protein, Drosophila; D009419:Nerve Tissue Proteins; C405164:Pins protein, Drosophila; C542608:ctp protein, Drosophila; D004398:Dyneins