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cAMP Signaling: An Important Event Facilitating Survival and Infectivity of Leishmania .
Author(s) -
Biswas Arunima,
Bhattacharya Arijit,
Vij Amit,
Das pijush
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.718.13
Subject(s) - phosphodiesterase , adenylate kinase , cyclase , protein kinase a , microbiology and biotechnology , biology , signal transduction , cytosol , camp dependent pathway , enzyme , biochemistry , oxidative phosphorylation , phosphodiesterase 3 , phosphorylation
Leishmania donovani encounters striking shift in temperature and pH and these act as the key environmental trigger for differentiation. Moreover, the parasite also faces a huge oxidative stress inside macrophages. We showed that differentiation condition‐exposed parasites become resistant to oxidative damage due to increased intracellular cAMP‐mediated responses. Objective For comprehensive understanding of cAMP signaling, we studied all the enzymes associated with cAMP metabolism, viz. the synthesizing enzyme adenylate cyclase, the degrading enzyme, phosphodiesterase (PDE), the regulatory enzyme pyrophosphatase and the functional enzyme, cAMP‐dependent protein kinase (PKA). Results A stage‐specific isoform of receptor adenylate cyclase (LdRACA) showed to regulate differentiation‐coupled induction of cAMP. The membrane bound acidocalcisomal pyrophosphatase, LdV‐H + PPase, was the major isoform regulating cAMP level in association with LdRACA by modulating the total pyrophosphate pool. A differentially expressed soluble cytosolic cAMP phosphodiesterase (LdPDEA) might be related to infection establishment by shifting trypanothione pool utilization bias toward antioxidant defence. Another cytosolic phosphodiesterase, LdPDED though not differentially expressed, was found to down‐regulate cAMP‐mediated responses by inhibiting catalytic activity of PKA and by increasing its own PDEase activity through phosphorylation. Also, a functional cAMP‐binding effector molecule (a regulatory subunit of PKA, LdPKAR) seemed to modulate metacyclogenesis through induction of autophagy. Conclusion This study reveals the significance of cAMP signaling in parasite survival and infectivity.