title: The transcriptomic signature of RacA activation and inactivation provides new insights into the morphogenetic network of Aspergillus niger.
abstract: RacA is the main Rho GTPase in Aspergillus niger regulating polarity maintenance via controlling actin dynamics. Both deletion and dominant activation of RacA (Rac(G18V)) provoke an actin localization defect and thereby loss of polarized tip extension, resulting in frequent dichotomous branching in the ΔracA strain and an apolar growing phenotype for Rac(G18V). In the current study the transcriptomics and physiological consequences of these morphological changes were investigated and compared with the data of the morphogenetic network model for the dichotomous branching mutant ramosa-1. This integrated approach revealed that polar tip growth is most likely orchestrated by the concerted activities of phospholipid signaling, sphingolipid signaling, TORC2 signaling, calcium signaling and CWI signaling pathways. The transcriptomic signatures and the reconstructed network model for all three morphology mutants (ΔracA, Rac(G18V), ramosa-1) imply that these pathways become integrated to bring about different physiological adaptations including changes in sterol, zinc and amino acid metabolism and changes in ion transport and protein trafficking. Finally, the fate of exocytotic (SncA) and endocytotic (AbpA, SlaB) markers in the dichotomous branching mutant ΔracA was followed, demonstrating that hyperbranching does not per se result in increased protein secretion.
authors.affiliation: Leiden University, Institute of Biology Leiden, Department Molecular Microbiology and Biotechnology, Leiden, The Netherlands.
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Nitsche
authors.forename: Mark
authors.initials: M
authors.lastname: Arentshorst
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Jørgensen
authors.forename: Arthur F J
authors.initials: AF
authors.lastname: Ram
authors.forename: Vera
authors.initials: V
authors.lastname: Meyer
mesh_terms: D001234:Aspergillus niger / Q000166:cytology* / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D059467:Transcriptome / Q000235:genetics*
chemical_list: D005656:Fungal Proteins
references.citation: Mol Cell. 2012 May 25;46(4):461-71
references.pmid: 22633490
references.citation: Mol Cell Biol. 2003 Jan;23(1):163-77
references.pmid: 12482970
references.citation: Mol Biol Cell. 2008 Apr;19(4):1439-49
references.pmid: 18216285
references.citation: Biochem J. 2005 Apr 15;387(Pt 2):489-96
references.pmid: 15588231
references.citation: Fungal Genet Biol. 1997 Dec;22(3):153-67
references.pmid: 9454643
references.citation: Biotechnol Bioeng. 1999 Nov 20;65(4):416-24
references.pmid: 10506417
references.citation: Mol Biol Cell. 2008 Jul;19(7):2885-96
references.pmid: 18417612
references.citation: Fungal Genet Biol. 2007 Dec;44(12):1310-23
references.pmid: 17590362
references.citation: Cell. 1996 Sep 20;86(6):865-75
references.pmid: 8808622
references.citation: J Biotechnol. 2007 Mar 10;128(4):770-5
references.pmid: 17275117
references.citation: Genetics. 1994 Feb;136(2):517-32
references.pmid: 8150280
references.citation: Mol Biol Cell. 2005 Jul;16(7):3128-39
references.pmid: 15872087
references.citation: Mol Microbiol. 2011 Mar;79(5):1151-67
references.pmid: 21205013
references.citation: Mol Biol Cell. 2007 Jan;18(1):295-312
references.pmid: 17093059
references.citation: Mol Cell Biol. 2005 Oct;25(19):8567-80
references.pmid: 16166638
references.citation: Nat Rev Microbiol. 2011 Nov 02;9(12):876-87
references.pmid: 22048737
references.citation: Arch Microbiol. 2005 May;183(4):292-300
references.pmid: 15812630
references.citation: Curr Opin Cell Biol. 2007 Aug;19(4):453-8
references.pmid: 17616384
references.citation: Appl Microbiol Biotechnol. 2005 Nov;69(1):44-50
references.pmid: 15909137
references.citation: Appl Microbiol Biotechnol. 2005 Dec;69(4):375-84
references.pmid: 16317480
references.citation: J Biol Chem. 2002 Mar 8;277(10):8588-96
references.pmid: 11779861
references.citation: Fungal Genet Biol. 2012 Aug;49(8):589-601
references.pmid: 22683653
references.citation: J Biol Chem. 2002 Sep 13;277(37):33749-57
references.pmid: 12095998
references.citation: Biotechnol Bioeng. 1999 Dec 20;65(6):638-48
references.pmid: 10550770
references.citation: Eukaryot Cell. 2006 Jun;5(6):881-95
references.pmid: 16757736
references.citation: Microbiology (Reading). 2012 Jan;158(Pt 1):46-57
references.pmid: 22053009
references.citation: Mol Biol Cell. 2010 Sep 1;21(17):3054-69
references.pmid: 20610658
references.citation: Biochim Biophys Acta. 2007 Mar;1771(3):322-30
references.pmid: 16807089
references.citation: Curr Genet. 1988 Nov;14(5):437-43
references.pmid: 3224384
references.citation: Mol Biol Cell. 2009 Mar;20(6):1618-28
references.pmid: 19158382
references.citation: J Biol Chem. 2004 May 7;279(19):19698-704
references.pmid: 14993228
references.citation: PLoS One. 2012;7(2):e31218
references.pmid: 22359575
references.citation: Mol Gen Genet. 1987 Jan;206(1):71-5
references.pmid: 3472035
references.citation: J Biol Chem. 2000 Jan 21;275(3):2191-8
references.pmid: 10636925
references.citation: Mol Cell Biol. 2001 Sep;21(18):6198-209
references.pmid: 11509663
references.citation: Nat Biotechnol. 2007 Feb;25(2):221-31
references.pmid: 17259976
references.citation: Biotechnol Adv. 2008 Mar-Apr;26(2):177-85
references.pmid: 18201856
references.citation: Mol Cell Biol. 2007 Jan;27(2):633-50
references.pmid: 17101780
references.citation: J Biol Chem. 2009 Aug 28;284(35):23860-71
references.pmid: 19581296
references.citation: Fungal Genet Biol. 2009 Mar;46 Suppl 1:S141-52
references.pmid: 18824119
references.citation: Mol Biol Cell. 2005 Apr;16(4):1883-900
references.pmid: 15689497
references.citation: Appl Environ Microbiol. 2002 Apr;68(4):1827-36
references.pmid: 11916702
references.citation: Fungal Genet Biol. 2004 Feb;41(2):213-25
references.pmid: 14732267
references.citation: Nat Rev Mol Cell Biol. 2006 Jun;7(6):404-14
references.pmid: 16723976
references.citation: Microbiology (Reading). 2000 Feb;146 ( Pt 2):415-426
references.pmid: 10708380
references.citation: Mol Biol Cell. 2006 Mar;17(3):1306-21
references.pmid: 16394103
references.citation: Mol Biol Cell. 2006 Mar;17(3):1218-27
references.pmid: 16394102
references.citation: Eukaryot Cell. 2008 Dec;7(12):2037-51
references.pmid: 18806210
references.citation: J Cell Biol. 2001 Oct 15;155(2):251-60
references.pmid: 11604420
references.citation: Biotechnol Bioeng. 2002 Mar 30;77(7):815-26
references.pmid: 11835142
references.citation: Trends Cell Biol. 2006 Jan;16(1):1-4
references.pmid: 16337381
references.citation: Mol Microbiol. 2011 Jul;81(1):40-55
references.pmid: 21564341
references.citation: Fungal Biol. 2011 Jun;115(6):518-40
references.pmid: 21640316
references.citation: Biotechnol Lett. 2011 Mar;33(3):469-76
references.pmid: 21088867
references.citation: Adv Biochem Eng Biotechnol. 2001;73:103-28
references.pmid: 11816809
references.citation: J Biol Chem. 2007 Aug 3;282(31):22775-85
references.pmid: 17553800
references.citation: Cell Microbiol. 2011 Feb;13(2):177-85
references.pmid: 21091925
references.citation: BMC Genomics. 2011 Oct 05;12:486
references.pmid: 21974739
references.citation: Methods Mol Biol. 2012;835:311-31
references.pmid: 22183662
references.citation: J Gen Microbiol. 1991 Aug;137(8):2017-23
references.pmid: 1955876
references.citation: J Cell Biol. 2011 May 30;193(5):901-16
references.pmid: 21624956
references.citation: Mol Microbiol. 2008 Feb;67(4):891-905
references.pmid: 18179595
references.citation: J Cell Sci. 2010 May 1;123(Pt 9):1578-87
references.pmid: 20388730
references.citation: Mol Syst Biol. 2010;6:349
references.pmid: 20160710
references.citation: Biochemistry. 2012 May 1;51(17):3675-83
references.pmid: 22475172
references.citation: Curr Genet. 2004 Jun;45(6):339-49
references.pmid: 15108020
references.citation: Appl Microbiol Biotechnol. 2010 Jul;87(4):1255-70
references.pmid: 20532762
references.citation: BMC Genomics. 2012 Aug 08;13:380
references.pmid: 22873931
references.citation: Fungal Genet Biol. 2008 Feb;45(2):152-64
references.pmid: 17826199
references.citation: Biotechnol Adv. 2004 Jan;22(3):189-259
references.pmid: 14665401
references.citation: Chem Phys Lipids. 1999 Apr;98(1-2):59-67
references.pmid: 10358928
references.citation: Microbiology (Reading). 2009 Aug;155(Pt 8):2714-2725
references.pmid: 19443549
references.citation: J Biol Chem. 2007 Nov 9;282(45):32935-48
references.pmid: 17804411
references.citation: Stat Appl Genet Mol Biol. 2004;3:Article3
references.pmid: 16646809
references.citation: J Biol Chem. 2008 Dec 5;283(49):34204-17
references.pmid: 18842580
references.citation: Mol Biol Cell. 2008 Mar;19(3):1113-24
references.pmid: 18184748
references.citation: Methods Enzymol. 2005;400:460-84
references.pmid: 16399365
references.citation: Eukaryot Cell. 2009 Nov;8(11):1677-91
references.pmid: 19749177
references.citation: Appl Environ Microbiol. 2010 Aug;76(16):5344-55
references.pmid: 20562270
references.citation: Nat Rev Mol Cell Biol. 2001 Feb;2(2):98-106
references.pmid: 11252968
references.citation: Appl Microbiol Biotechnol. 2010 Jul;87(4):1463-73
references.pmid: 20422182