title: Role of actin cytoskeletal dynamics in activation of the cyclic AMP pathway and HWP1 gene expression in Candida albicans.
abstract: Changes in gene expression during reversible bud-hypha transitions of the opportunistic fungal pathogen Candida albicans permit adaptation to environmental conditions that are critical for proliferation in host tissues. Our previous work has shown that the hypha-specific adhesin gene HWP1 is up-regulated by the cyclic AMP (cAMP) signaling pathway. However, little is known about the potential influences of determinants of cell morphology on HWP1 gene expression. We found that blocking hypha formation with cytochalasin A, which destabilizes actin filaments, and with latrunculin A, which sequesters actin monomers, led to a loss of HWP1 gene expression. In contrast, high levels of HWP1 gene expression were observed when the F-actin stabilizer jasplakinolide was used to block hypha formation, suggesting that HWP1 expression could be regulated by actin structures. Mutants defective in formin-mediated nucleation of F-actin were reduced in HWP1 gene expression, providing genetic support for the importance of actin structures. Kinetic experiments with wild-type and actin-deficient cells revealed two distinct phases of HWP1 gene expression, with a slow, actin-independent phase preceding a fast, actin-dependent phase. Low levels of HWP1 gene expression that appeared to be independent of stabilized actin and cAMP signaling were detected using indirect immunofluorescence. A connection between actin structures and the cAMP signaling pathway was shown using hyper- and hypomorphic cAMP mutants, providing a possible mechanism for up-regulation of HWP1 gene expression by stabilized actin. The results reveal a new role for F-actin as a regulatory agent of hypha-specific gene expression at the bud-hypha transition.
authors: Microbiology and Molecular Pathogenesis Program, Dartmouth Medical School, Vail Building, HB7550, Hanover, NH 03755, USA.
authors: Michael J
authors: MJ
authors: Wolyniak
authors: Paula
authors: P
authors: Sundstrom
mesh_terms: D000199:Actins / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D016764:Cell Polarity / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D047630:Depsipeptides / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D025301:Hyphae / Q000166:cytology / Q000187:drug effects; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003572:Cytochalasins; D047630:Depsipeptides; D005656:Fungal Proteins; C118102:HWP1 protein, Candida albicans; D008562:Membrane Glycoproteins; D053778:Thiazolidines; C057531:jasplakinolide; C031218:cytochalasin A; D000242:Cyclic AMP; C037067:latrunculin A
references: Eukaryot Cell. 2006 Aug;5(8):1252-65
references: 16896210
references: Mol Cell Biol. 2006 Sep;26(17):6487-501
references: 16914733
references: Microbiol Mol Biol Rev. 2006 Sep;70(3):605-45
references: 16959963
references: Mol Biol Cell. 2006 Oct;17(10):4364-78
references: 16855023
references: Mol Microbiol. 2006 Nov;62(4):997-1013
references: 17038117
references: Eukaryot Cell. 2007 Apr;6(4):693-709
references: 17220463
references: Eukaryot Cell. 2007 Apr;6(4):682-92
references: 17277173
references: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D358-63
references: 15608216
references: Infect Immun. 2005 Feb;73(2):1239-42
references: 15664973
references: Curr Biol. 2005 Apr 26;15(8):724-31
references: 15854904
references: J Cell Sci. 2005 May 15;118(Pt 10):2119-32
references: 15855235
references: Mol Biol Cell. 2005 Jun;16(6):2903-12
references: 15814840
references: J Cell Sci. 2005 Jun 15;118(Pt 12):2637-48
references: 15914538
references: Curr Biol. 2005 Jun 21;15(12):1150-5
references: 15964282
references: Eukaryot Cell. 2005 Aug;4(8):1493-502
references: 16087754
references: Cell Microbiol. 2005 Nov;7(11):1546-54
references: 16207242
references: Eukaryot Cell. 2005 Oct;4(10):1712-24
references: 16215178
references: Mol Biol Cell. 2006 Jan;17(1):295-307
references: 16267276
references: Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):726-31
references: 16407097
references: J Mol Biol. 2007 Jul 6;370(2):331-48
references: 17521670
references: J Cell Sci. 2005 Jul 1;118(Pt 13):2935-47
references: 15976451
references: Arch Dermatol Res. 2000 May;292(5):260-4
references: 10867815
references: Yeast. 2000 Oct;16(14):1313-23
references: 11015728
references: Mol Cell Biol. 2001 Jan;21(1):235-48
references: 11113198
references: Curr Opin Microbiol. 2000 Dec;3(6):582-8
references: 11121777
references: Curr Biol. 2000 Dec 14-28;10(24):1587-90
references: 11137010
references: J Bacteriol. 2001 May;183(10):3211-23
references: 11325951
references: Mol Cell Biol. 2001 Oct;21(19):6418-28
references: 11533231
references: Curr Opin Microbiol. 2001 Dec;4(6):728-35
references: 11731326
references: J Biol Chem. 2001 Dec 28;276(52):48988-96
references: 11595734
references: Mol Biol Cell. 2002 Jan;13(1):134-45
references: 11809828
references: Nat Cell Biol. 2002 Mar;4(3):260-9
references: 11875440
references: Mol Microbiol. 2002 Oct;46(1):269-80
references: 12366849
references: Antimicrob Agents Chemother. 2002 Nov;46(11):3617-20
references: 12384374
references: Mol Biol Cell. 2002 Oct;13(10):3452-65
references: 12388749
references: Eukaryot Cell. 2002 Apr;1(2):213-28
references: 12455956
references: Eukaryot Cell. 2002 Feb;1(1):95-104
references: 12455975
references: J Biol Chem. 2002 Dec 27;277(52):50683-92
references: 12388543
references: J Cell Biol. 2003 Feb 3;160(3):409-21
references: 12566431
references: Microbiology. 2003 Oct;149(Pt 10):2977-86
references: 14523129
references: Mol Microbiol. 2003 Oct;50(2):391-409
references: 14617167
references: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14327-32
references: 14623979
references: Biochemistry. 2004 Jun 1;43(21):6645-55
references: 15157098
references: Eukaryot Cell. 2004 Jun;3(3):724-34
references: 15189993
references: Mol Biol Cell. 2004 Aug;15(8):3658-72
references: 15155805
references: J Biol Chem. 2004 Sep 24;279(39):40737-47
references: 15262971
references: Gene. 2004 Oct 27;341:119-27
references: 15474295
references: Mol Biol Cell. 2004 Nov;15(11):5158-71
references: 15356265
references: Infect Immun. 1975 May;11(5):1014-23
references: 1091557
references: Biochim Biophys Acta. 1975 Apr 21;389(1):145-53
references: 124588
references: Biochem Biophys Res Commun. 1976 Dec 6;73(3):727-32
references: 1008884
references: Infect Immun. 1984 Mar;43(3):850-5
references: 6199304
references: Mol Gen Genet. 1984;198(2):179-82
references: 6394964
references: J Gen Microbiol. 1986 Jul;132(7):2035-47
references: 3540192
references: J Cell Biol. 1988 Jun;106(6):1955-71
references: 3290222
references: Antimicrob Agents Chemother. 1988 Aug;32(8):1154-7
references: 3190203
references: Life Sci. 1988;43(22):1825-30
references: 3200109
references: Cell. 1989 Mar 10;56(5):801-13
references: 2647301
references: Int J Immunopharmacol. 1989;11(5):459-65
references: 2807624
references: Cell. 1990 Apr 20;61(2):329-40
references: 2158860
references: Cell Motil Cytoskeleton. 1990;16(3):182-9
references: 1973080
references: FEBS Lett. 1991 Aug 5;287(1-2):175-7
references: 1879528
references: J Cell Biol. 1992 Mar;116(5):1071-80
references: 1740466
references: Genetics. 1993 Jul;134(3):717-28
references: 8349105
references: J Cell Biol. 1993 Dec;123(6 Pt 2):1789-96
references: 8276897
references: Microbiology. 1994 Feb;140 ( Pt 2):271-80
references: 8180692
references: J Biol Chem. 1994 May 27;269(21):14869-71
references: 8195116
references: Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5686-9
references: 8202549
references: Yeast. 1994 Mar;10(3):355-70
references: 8017105
references: J Biol Chem. 1996 Mar 15;271(11):6298-305
references: 8626424
references: Mol Biol Cell. 1997 Feb;8(2):367-85
references: 9190214
references: Science. 1997 Apr 4;276(5309):118-22
references: 9082982
references: Yeast. 1997 Jul;13(9):871-80
references: 9234675
references: J Cell Biol. 1998 Sep 21;142(6):1501-17
references: 9744880
references: Microbiol Mol Biol Rev. 1999 Mar;63(1):54-105
references: 10066831
references: J Bacteriol. 1999 Sep;181(17):5273-9
references: 10464197
references: Int J Med Microbiol. 2005 Jun;295(2):121-7
references: 15969473
references: Microbiology. 2005 Aug;151(Pt 8):2623-36
references: 16079341