title: Function and regulation of Tumbleweed (RacGAP50C) in neuroblast proliferation and neuronal morphogenesis.
abstract: Drosophila RacGAP50C and its homologues act as part of a complex with a kinesin-like protein (Pavarotti/Zen-4) that is essential for the formation of the central spindle and completion of cytokinesis [Mishima, M., Kaitna, S. & Glotzer, M. (2002) Dev. Cell 2, 41-54; Somers, W. G. & Saint, R. (2003) Dev. Cell 4, 29-39; Jantsch-Plunger et al. (2000) J. Cell Biol. 149, 1391-1404]. We report here that RacGAP50C corresponds to the tumbleweed (tum) gene previously identified based on its defects in dendrite development of sensory neurons [Gao, F. B., Brenman, J. E., Jan, L. Y. & Jan, Y. N. (1999) Genes Dev. 13, 2549-2561]. Using mushroom body neurogenesis and morphogenesis as a model, we show that Tumbleweed (Tum), Pavarotti, and their association are required for neuroblast proliferation. Tum with a mutation predicted to disrupt the GTPase-activating protein (GAP) activity still largely retains its activity in regulating cell division but is impaired in its activity to limit axon growth. We also provide evidence that Tum and Pavarotti regulate the subcellular localization of each other in postmitotic neurons and that cytoplasmic accumulation of both proteins disrupts axon development in a GAP-dependent manner. Taken together with previous studies of RacGAP50C in regulating cytokinesis, we propose that Tum serves as a scaffolding protein in regulating cell division but acts as a GAP to limit axon growth in postmitotic neurons.
authors.affiliation: Department of Biological Sciences and Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ann Y N
authors.initials: AY
authors.lastname: Goldstein
authors.forename: Yuh-Nung
authors.initials: YN
authors.lastname: Jan
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D049109:Cell Proliferation; D003712:Dendrites / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology; D009024:Morphogenesis; D009474:Neurons / Q000502:physiology*; D034622:RNA Interference
chemical_list: D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D008869:Microtubule-Associated Proteins; C490516:pav protein, Drosophila; C085379:rho GTPase-activating protein
references.citation: Neuron. 2000 Feb;25(2):307-16
references.pmid: 10719887
references.citation: J Cell Biol. 2000 Jun 26;149(7):1391-404
references.pmid: 10871280
references.citation: J Neurosci. 2000 Aug 1;20(15):5782-91
references.pmid: 10908619
references.citation: Blood. 2000 Sep 15;96(6):2116-24
references.pmid: 10979956
references.citation: Development. 2000 Dec;127(24):5427-38
references.pmid: 11076763
references.citation: J Biol Chem. 2001 Feb 23;276(8):5821-8
references.pmid: 11085985
references.citation: Science. 2001 Feb 16;291(5507):1304-51
references.pmid: 11181995
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011
references.citation: Mech Dev. 2001 Apr;102(1-2):33-44
references.pmid: 11287179
references.citation: Cell. 2001 Oct 19;107(2):195-207
references.pmid: 11672527
references.citation: Science. 2001 Nov 9;294(5545):1299-304
references.pmid: 11701921
references.citation: Dev Cell. 2002 Jan;2(1):41-54
references.pmid: 11782313
references.citation: J Cell Sci. 2002 Feb 15;115(Pt 4):725-36
references.pmid: 11865028
references.citation: Nature. 2002 Mar 28;416(6879):442-7
references.pmid: 11919635
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11754-9
references.pmid: 12195014
references.citation: Nucleic Acids Res. 2003 Jan 1;31(1):172-5
references.pmid: 12519974
references.citation: Dev Cell. 2003 Jan;4(1):29-39
references.pmid: 12530961
references.citation: Development. 2003 Mar;130(6):1203-13
references.pmid: 12571111
references.citation: Nat Rev Neurosci. 2003 Apr;4(4):266-75
references.pmid: 12671643
references.citation: Dev Cell. 2003 Apr;4(4):549-60
references.pmid: 12689593
references.citation: J Neurosci. 2003 Apr 15;23(8):3118-23
references.pmid: 12716918
references.citation: Mol Biol Cell. 2003 Oct;14(10):4028-38
references.pmid: 14517316
references.citation: Curr Biol. 2004 Jun 8;14(11):932-41
references.pmid: 15182666
references.citation: Nature. 2004 Aug 19;430(7002):908-13
references.pmid: 15282614
references.citation: Development. 1997 Feb;124(4):761-71
references.pmid: 9043058
references.citation: Science. 1997 Jul 18;277(5324):333-8
references.pmid: 9219684
references.citation: J Biol Chem. 1997 Dec 26;272(52):32830-5
references.pmid: 9407060
references.citation: J Biol Chem. 1998 Mar 13;273(11):6019-23
references.pmid: 9497316
references.citation: Nature. 1998 Apr 30;392(6679):923-6
references.pmid: 9582072
references.citation: Genes Dev. 1998 May 15;12(10):1483-94
references.pmid: 9585508
references.citation: Neuron. 1999 Mar;22(3):451-61
references.pmid: 10197526
references.citation: Learn Mem. 1998 May-Jun;5(1-2):38-51
references.pmid: 10454371
references.citation: Development. 1999 Sep;126(18):4065-76
references.pmid: 10457015
references.citation: Genes Dev. 1999 Sep 1;13(17):2301-14
references.pmid: 10485851
references.citation: Genes Dev. 1999 Oct 1;13(19):2549-61
references.pmid: 10521399
references.citation: Neuron. 2004 Dec 2;44(5):779-93
references.pmid: 15572110