title: Role of cAMP Signaling in the Survival and Infectivity of the Protozoan Parasite, Leishmania donovani.
abstract: Leishmania donovani, while invading macrophages, encounters striking shift in temperature and pH (from 22°C and pH 7.2 to 37°C and pH 5.5), which act as the key environmental trigger for differentiation, and increases cAMP level and cAMP-mediated responses. For comprehensive understanding of cAMP signaling, we studied the enzymes related to cAMP metabolism. A stage-specific and developmentally regulated isoform of receptor adenylate cyclase (LdRACA) showed to regulate differentiation-coupled induction of cAMP. The soluble acidocalcisomal pyrophosphatase, Ldvsp1, was the major isoform regulating cAMP level in association with LdRACA. A differentially expressed soluble cytosolic cAMP phosphodiesterase (LdPDEA) might be related to infection establishment by shifting trypanothione pool utilization bias toward antioxidant defense. We identified and cloned a functional cAMP-binding effector molecule from L. donovani (a regulatory subunit of cAMP-dependent protein kinase, LdPKAR) that may modulate metacyclogenesis through induction of autophagy. This study reveals the significance of cAMP signaling in parasite survival and infectivity.
authors.affiliation: Molecular Cell Biology Laboratory, Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata 700032, India.
authors.forename: Arunima
authors.initials: A
authors.lastname: Biswas
authors.forename: Arijit
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Pijush K
authors.initials: PK
authors.lastname: Das
references.citation: BMC Microbiol. 2006 Mar 08;6:25
references.pmid: 16522215
references.citation: Mol Biochem Parasitol. 1981 May;3(1):19-31
references.pmid: 6265773
references.citation: Nature. 1980 Jul 31;286(5772):490-2
references.pmid: 6250067
references.citation: Antimicrob Agents Chemother. 1997 May;41(5):1064-8
references.pmid: 9145870
references.citation: Mol Biochem Parasitol. 2006 Oct;149(2):242-5
references.pmid: 16815565
references.citation: J Physiol. 2002 Aug 1;542(Pt 3):795-801
references.pmid: 12154179
references.citation: J Clin Invest. 1991 Nov;88(5):1511-21
references.pmid: 1658042
references.citation: Hum Mol Genet. 2006 Oct 1;15(19):2962-71
references.pmid: 16963469
references.citation: J Immunol. 2001 Jul 15;167(2):893-901
references.pmid: 11441096
references.citation: EMBO J. 1998 May 15;17(10):2838-45
references.pmid: 9582277
references.citation: Mol Biochem Parasitol. 1996 May;77(2):201-15
references.pmid: 8813666
references.citation: Gene. 2002 Apr 17;288(1-2):65-75
references.pmid: 12034495
references.citation: Genetics. 2005 Mar;169(3):1203-14
references.pmid: 15545649
references.citation: Free Radic Biol Med. 2008 Mar 1;44(5):779-94
references.pmid: 18078824
references.citation: J Biol Chem. 1995 Jul 21;270(29):17551-8
references.pmid: 7615561
references.citation: Mol Cell Biol. 2004 Jan;24(1):338-51
references.pmid: 14673167
references.citation: J Biol Chem. 2001 Sep 7;276(36):34279-87
references.pmid: 11438539
references.citation: J Cell Sci. 2008 Mar 1;121(Pt 5):561-70
references.pmid: 18252798
references.citation: J Biol Chem. 2006 Apr 21;281(16):11384-96
references.pmid: 16497676
references.citation: Mol Biochem Parasitol. 1998 Sep 1;95(1):9-20
references.pmid: 9763285
references.citation: Curr Mol Med. 2004 Sep;4(6):585-99
references.pmid: 15357210
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5311-6
references.pmid: 9560272
references.citation: EMBO J. 1998 Jul 1;17(13):3556-64
references.pmid: 9649426
references.citation: Biochem J. 2003 Feb 1;369(Pt 3):447-52
references.pmid: 12459037
references.citation: Proc Natl Acad Sci U S A. 1998 May 12;95(10):5684-9
references.pmid: 9576944
references.citation: J Biol Chem. 2000 Oct 27;275(43):33883-9
references.pmid: 10931831
references.citation: Autophagy. 2007 Mar-Apr;3(2):151-3
references.pmid: 17204847
references.citation: PLoS Pathog. 2008 Feb 8;4(2):e19
references.pmid: 18248092
references.citation: Mol Cell. 2006 Nov 3;24(3):383-95
references.pmid: 17081989
references.citation: Mol Microbiol. 1998 Jul;29(2):653-60
references.pmid: 9720880
references.citation: Free Radic Biol Med. 2009 Nov 15;47(10):1494-506
references.pmid: 19733234
references.citation: Infect Immun. 2003 Oct;71(10):5910-20
references.pmid: 14500512
references.citation: Mol Biochem Parasitol. 2005 May;141(1):99-108
references.pmid: 15811531
references.citation: J Immunol. 1983 Oct;131(4):1994-9
references.pmid: 6619546
references.citation: Mol Microbiol. 2012 Feb;83(3):548-64
references.pmid: 22168343