Rho1 regulates apoptosis via activation of the JNK signaling pathway at the plasma membrane.
Precisely controlled growth and morphogenesis of developing epithelial tissues require coordination of multiple factors, including proliferation, adhesion, cell shape, and apoptosis. RhoA, a small GTPase, is known to control epithelial morphogenesis and integrity through its ability to regulate the cytoskeleton. In this study, we examine a less well-characterized RhoA function in cell survival. We demonstrate that the Drosophila melanogaster RhoA, Rho1, promotes apoptosis independently of Rho kinase through its effects on c-Jun NH(2)-terminal kinase (JNK) signaling. In addition, Rho1 forms a complex with Slipper (Slpr), an upstream activator of the JNK pathway. Loss of Moesin (Moe), an upstream regulator of Rho1 activity, results in increased levels of Rho1 at the plasma membrane and cortical accumulation of Slpr. Together, these results suggest that Rho1 functions at the cell cortex to regulate JNK activity and implicate Rho1 and Moe in epithelial cell survival.
Neisch
Amanda L
AL
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Speck
Olga
O
Stronach
Beth
B
Fehon
Richard G
RG
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000502:physiology; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D014921:Wings, Animal / Q000033:anatomy & histology / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D008565:Membrane Proteins; C099886:moesin, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C447860:slpr protein, Drosophila; C511153:Rho1 protein, Drosophila; D020741:rho GTP-Binding Proteins
Nucleic Acids Res. 1996 Nov 1;24(21):4362-3
8932397
Exp Cell Res. 2004 May 1;295(2):300-14
15093731
Genes Dev. 1990 Nov;4(11):2011-23
2177439
J Cell Biol. 2006 Oct 23;175(2):305-13
17060498
Genetics. 2006 Oct;174(2):719-33
16888342
Dev Cell. 2004 Jun;6(6):855-64
15177033
Blood. 2008 Mar 15;111(6):3163-72
18182570
J Biol Chem. 1996 Nov 1;271(44):27225-8
8910292
Annu Rev Pharmacol Toxicol. 2008;48:199-225
17883330
Oncogene. 2010 Mar 4;29(9):1374-83
19935704
Dev Cell. 2004 Jun;6(6):865-73
15177034
Med Mol Morphol. 2005 Mar;38(1):18-22
16158175
Development. 2006 Sep;133(17):3349-57
16887822
Nat Rev Mol Cell Biol. 2002 Aug;3(8):586-99
12154370
Mol Cell Biol. 2000 May;20(9):3015-26
10757786
Oncogene. 1998 Jun 25;16(25):3279-84
9681826
J Biol Chem. 1995 Dec 8;270(49):29071-4
7493928
Genes Dev. 1998 Feb 15;12(4):557-70
9472024
Cell. 2004 Apr 2;117(1):117-29
15066287
J Cell Biol. 2007 Oct 8;179(1):23-31
17908916
Int J Dev Biol. 2004 Dec;48(10):1087-94
15602694
J Cell Sci. 2009 Jun 15;122(Pt 12):1939-46
19494121
EMBO J. 2002 Jun 17;21(12):3009-18
12065414
EMBO J. 2003 Jan 15;22(2):252-61
12514131
EMBO J. 2007 Jan 24;26(2):380-90
17183370
Trends Cell Biol. 2005 Dec;15(12):651-8
16243528
Curr Biol. 2006 Jun 6;16(11):1139-46
16753569
Cell. 1995 Nov 3;83(3):451-61
8521475
Genetics. 2000 Jul;155(3):1253-65
10880486
EMBO J. 2006 Nov 15;25(22):5294-304
17082773
Development. 2005 Sep;132(17):3935-46
16079158
Curr Biol. 2002 Jul 23;12(14):1263-8
12176339
Development. 2000 May;127(9):1887-97
10751177
Dev Biol. 2002 Nov 1;251(1):74-90
12413899
Dev Biol. 2000 May 1;221(1):181-94
10772800
Genes Dev. 2004 Mar 1;18(5):584-94
15037551
Curr Biol. 2008 Jan 22;18(2):91-101
18207738
BMC Cell Biol. 2006 Feb 01;7:7
16451733
EMBO J. 2007 Jan 10;26(1):209-20
17159908
Genes Genet Syst. 2006 Apr;81(2):129-34
16755136
PLoS Biol. 2003 Nov;1(2):E35
14624240
Nat Rev Mol Cell Biol. 2002 Sep;3(9):663-72
12209126
Mol Biol Cell. 2007 Dec;18(12):4780-93
17881735
Dev Cell. 2006 Jan;10(1):33-44
16399076
Development. 2004 Feb;131(4):725-32
14724125
Development. 1999 Dec;126(23):5453-62
10556069
Dev Biol. 2005 Jun 1;282(1):163-73
15936337
Dev Biol. 2006 Jul 1;295(1):178-93
16643887
Neuron. 2006 Jul 6;51(1):57-69
16815332
Nat Cell Biol. 2002 Jun;4(6):439-44
12021770
J Biol Chem. 2000 May 12;275(19):14231-41
10799501
Mech Dev. 2006 May;123(5):337-51
16682173
Genes Cells. 2006 Apr;11(4):397-407
16611243
Mol Biol Cell. 2007 Apr;18(4):1242-52
17267693
Nat Cell Biol. 2002 Jun;4(6):416-24
12021767
J Cell Biol. 2005 Oct 10;171(1):143-52
16216927
Genes Dev. 1999 May 1;13(9):1168-80
10323867
Development. 2002 Jul;129(13):3173-83
12070092
Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7300-5
10377409
Genes Dev. 2002 Feb 1;16(3):377-87
11825878
J Cell Biol. 2008 Feb 25;180(4):739-46
18283112
Genes Dev. 2004 Sep 15;18(18):2243-8
15371338
J Biol Chem. 1997 Sep 12;272(37):23371-5
9287351
Genetics. 2005 Dec;171(4):1683-94
16079232
EMBO J. 1998 Mar 2;17(5):1395-404
9482736
Nat Cell Biol. 2002 Sep;4(9):705-10
12198495
Nature. 2003 Jan 2;421(6918):83-7
12511959
J Cell Biol. 1998 Feb 9;140(3):647-57
9456324
Dev Biol. 2005 Oct 1;286(1):256-69
16125690
Biochem J. 2005 Aug 15;390(Pt 1):1-9
16083425
EMBO J. 2000 Oct 2;19(19):5123-34
11013215
Oncogene. 2007 May 14;26(22):3185-202
17496915
Cell. 2001 Apr 6;105(1):81-91
11301004