Function and regulation of Tumbleweed (RacGAP50C) in neuroblast proliferation and neuronal morphogenesis.
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.
Goldstein
Ann Y N
AY
Department of Biological Sciences and Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
Jan
Yuh-Nung
YN
Luo
Liqun
L
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
D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D008869:Microtubule-Associated Proteins; C490516:pav protein, Drosophila; C085379:rho GTPase-activating protein
Neuron. 2000 Feb;25(2):307-16
10719887
J Cell Biol. 2000 Jun 26;149(7):1391-404
10871280
J Neurosci. 2000 Aug 1;20(15):5782-91
10908619
Blood. 2000 Sep 15;96(6):2116-24
10979956
Development. 2000 Dec;127(24):5427-38
11076763
J Biol Chem. 2001 Feb 23;276(8):5821-8
11085985
Science. 2001 Feb 16;291(5507):1304-51
11181995
Nature. 2001 Feb 15;409(6822):860-921
11237011
Mech Dev. 2001 Apr;102(1-2):33-44
11287179
Cell. 2001 Oct 19;107(2):195-207
11672527
Science. 2001 Nov 9;294(5545):1299-304
11701921
Dev Cell. 2002 Jan;2(1):41-54
11782313
J Cell Sci. 2002 Feb 15;115(Pt 4):725-36
11865028
Nature. 2002 Mar 28;416(6879):442-7
11919635
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11754-9
12195014
Nucleic Acids Res. 2003 Jan 1;31(1):172-5
12519974
Dev Cell. 2003 Jan;4(1):29-39
12530961
Development. 2003 Mar;130(6):1203-13
12571111
Nat Rev Neurosci. 2003 Apr;4(4):266-75
12671643
Dev Cell. 2003 Apr;4(4):549-60
12689593
J Neurosci. 2003 Apr 15;23(8):3118-23
12716918
Mol Biol Cell. 2003 Oct;14(10):4028-38
14517316
Curr Biol. 2004 Jun 8;14(11):932-41
15182666
Nature. 2004 Aug 19;430(7002):908-13
15282614
Development. 1997 Feb;124(4):761-71
9043058
Science. 1997 Jul 18;277(5324):333-8
9219684
J Biol Chem. 1997 Dec 26;272(52):32830-5
9407060
J Biol Chem. 1998 Mar 13;273(11):6019-23
9497316
Nature. 1998 Apr 30;392(6679):923-6
9582072
Genes Dev. 1998 May 15;12(10):1483-94
9585508
Neuron. 1999 Mar;22(3):451-61
10197526
Learn Mem. 1998 May-Jun;5(1-2):38-51
10454371
Development. 1999 Sep;126(18):4065-76
10457015
Genes Dev. 1999 Sep 1;13(17):2301-14
10485851
Genes Dev. 1999 Oct 1;13(19):2549-61
10521399
Neuron. 2004 Dec 2;44(5):779-93
15572110