Mds3 regulates morphogenesis in Candida albicans through the TOR pathway.
The success of Candida albicans as a major human fungal pathogen is dependent on its ability to colonize and survive as a commensal on diverse mucosal surfaces. One trait required for survival and virulence in the host is the morphogenetic yeast-to-hypha transition. Mds3 was identified as a regulator of pH-dependent morphogenesis that functions in parallel with the classic Rim101 pH-sensing pathway. Microarray analyses revealed that mds3 Delta/Delta cells had an expression profile indicative of a hyperactive TOR pathway, including the preferential expression of genes encoding ribosomal proteins and a decreased expression of genes involved in nitrogen source utilization. The transcriptional and morphological defects of the mds3 Delta/Delta mutant were rescued by rapamycin, an inhibitor of TOR, and this rescue was lost in strains carrying the rapamycin-resistant TOR1-1 allele or an rbp1 Delta/Delta deletion. Rapamycin also rescued the transcriptional and morphological defects associated with the loss of Sit4, a TOR pathway effector, but not the loss of Rim101 or Ras1. The sit4 Delta/Delta and mds3 Delta/Delta mutants had additional phenotypic similarities, suggesting that Sit4 and Mds3 function similarly in the TOR pathway. Finally, we found that Mds3 and Sit4 coimmunoprecipitate. Thus, Mds3 is a new member of the TOR pathway that contributes to morphogenesis in C. albicans as a regulator of this key morphogenetic pathway.
Zacchi
Lucia F
LF
Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Gomez-Raja
Jonatan
J
Davis
Dana A
DA
D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D017931:DNA Primers / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D006801:Humans; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology
D017931:DNA Primers; D004271:DNA, Fungal; D005656:Fungal Proteins; D020123:Sirolimus
Mol Cell Biol. 2004 Jan;24(1):338-51
14673167
Mol Cell Biol. 2000 Feb;20(3):971-8
10629054
Mol Cell Biol. 1993 Oct;13(10):6012-23
8413204
Cell. 1997 Sep 5;90(5):939-49
9298905
J Cell Biol. 2004 Jun 7;165(5):697-707
15184402
Mol Cell Biol. 1996 Jun;16(6):2744-55
8649382
Curr Opin Microbiol. 2004 Aug;7(4):350-7
15358253
Genes Dev. 1999 Dec 15;13(24):3271-9
10617575
J Cell Biol. 2003 Apr 28;161(2):333-47
12719473
Cell. 2006 Feb 10;124(3):471-84
16469695
J Bacteriol. 1999 Dec;181(24):7524-30
10601210
FEMS Microbiol Lett. 2009 Jun;295(1):1-9
19473245
EMBO J. 1999 May 17;18(10):2782-92
10329624
Cell Microbiol. 2005 Nov;7(11):1546-54
16207242
J Cell Biol. 1994 Oct;127(2):373-86
7929582
PLoS Pathog. 2006 Jul;2(7):e63
16839200
Curr Biol. 2000 Dec 14-28;10(24):1574-81
11137008
Oncogene. 2006 Oct 16;25(48):6373-83
17041623
J Biol Chem. 2001 Mar 9;276(10):7027-32
11096119
Mol Microbiol. 2008 Jul;69(1):201-17
18466294
Curr Top Microbiol Immunol. 2004;279:53-72
14560951
PLoS Pathog. 2009 Feb;5(2):e1000294
19197361
Trends Cell Biol. 2000 Jan;10(1):17-24
10603472
Mol Cell. 2002 Jul;10(1):163-73
12150916
Clin Microbiol Infect. 2009 Jan;15 Suppl 1:17-9
19220347
Mol Cell Biol. 2002 Nov;22(21):7428-38
12370290
Genetics. 1997 Nov;147(3):1351-66
9383076
Mol Cell. 2003 Apr;11(4):895-904
12718876
Infect Immun. 2000 Oct;68(10):5953-9
10992507
Sci STKE. 2003 Jul 15;2003(191):PE27
12865498
Curr Top Microbiol Immunol. 2004;279:19-38
14560949
Eukaryot Cell. 2005 Nov;4(11):1794-800
16278446
J Bacteriol. 1999 Oct;181(20):6339-46
10515923
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14866-70
10611304
Eukaryot Cell. 2005 Jan;4(1):63-71
15643061
Microbiol Rev. 1995 Jun;59(2):304-22
7603412
J Biol Chem. 2009 Jan 23;284(4):2522-34
19015262
Nature. 2006 Sep 28;443(7110):415-20
17006507
EMBO J. 2001 Sep 3;20(17):4742-52
11532938
Microbiology (Reading). 2003 Dec;149(Pt 12):3629-3637
14663094
Cell. 1993 Jul 16;74(1):205-14
8334704
Science. 2005 Aug 5;309(5736):938-40
16081737
Science. 1994 Dec 9;266(5191):1723-6
7992058
Genetics. 2002 Dec;162(4):1573-81
12524333
Mol Cell Neurosci. 2008 Sep;39(1):118-24
18620060
Immunity. 2009 Jun 19;30(6):832-44
19538929
Mol Microbiol. 2004 Feb;51(3):691-709
14731272
Cell Cycle. 2006 Dec;5(23):2729-32
17172843
Cell. 2002 Jul 26;110(2):163-75
12150925
Genetics. 2009 Feb;181(2):511-23
19087957
Nature. 2002 Jan 10;415(6868):141-7
11805826
Nature. 2006 Mar 30;440(7084):631-6
16429126
Mol Biol Cell. 2001 Dec;12(12):4103-13
11739804
J Bacteriol. 1999 Dec;181(24):7516-23
10601209
J Antibiot (Tokyo). 1975 Oct;28(10):721-6
1102508
Antimicrob Agents Chemother. 2001 Nov;45(11):3162-70
11600372
Yeast. 2009 Jul;26(7):399-406
19504625
Mol Cell. 2002 Sep;10(3):457-68
12408816
Curr Opin Microbiol. 1998 Dec;1(6):687-92
10066539
Curr Opin Microbiol. 2009 Aug;12(4):365-70
19632143
Mol Microbiol. 2007 Nov;66(4):858-71
17927701
Curr Opin Microbiol. 2002 Aug;5(4):366-71
12160854
Curr Biol. 2007 Jun 19;17(12):1007-13
17540568
Genes Dev. 1996 Aug 1;10(15):1904-16
8756348
Curr Med Chem. 2008;15(12):1192-208
18473813
Eukaryot Cell. 2005 Aug;4(8):1493-502
16087754
Science. 1991 Aug 23;253(5022):905-9
1715094
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6784-9
11997479
Mol Microbiol. 2001 Nov;42(3):673-87
11722734
Cell Microbiol. 2008 Nov;10(11):2180-96
18627379
J Biol Chem. 2004 Mar 12;279(11):10270-8
14679193
J Bacteriol. 1999 Mar;181(6):1868-74
10074081
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3070-5
9096347
Genetics. 2009 Mar;181(3):861-74
19104072
Mol Microbiol. 2004 Dec;54(5):1335-51
15554973
Mol Cell. 2003 Jun;11(6):1467-78
12820961
J Biol Chem. 1999 Feb 12;274(7):4266-72
9933627
Am J Physiol Cell Physiol. 2004 Mar;286(3):C507-17
14592809
Mol Cell. 2008 Mar 14;29(5):552-62
18342603