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Identification of a Protein Kinase A Regulatory Subunit from Leishmania having Importance in Metacyclogenesis Through Induction of Autophagy

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Title Identification of a Protein Kinase A Regulatory Subunit from
Leishmania having Importance in Metacyclogenesis Through
Induction of Autophagy
 
Creator Bhattacharya, Arijit
Biswas, Arunima
Das, Pijush K
 
Subject Infectious Diseases and Immunology
 
Description cAMP-mediated responses act as modulators of environmental
sensing and cellular differentiation of many
kinetoplastidae parasites including Leishmania.
Although cAMP synthesizing (adenylate cyclase) and
degrading (phosphodiesterase) enzymes have been
cloned and characterized from Leishmania, no cAMPbinding
effector molecule has yet been identified from
this parasite. In this study, a regulatory subunit of
cAMP-dependent protein kinase (Ldpkar1), homologous
to mammalian class I cAMP-dependent protein
kinase regulatory subunit, has been identified from
L. donovani. Further characterization suggested possible
interaction of LdPKAR1 with PKA catalytic
subunits and inhibition of PKAactivity. This PKAregulatory
subunit is expressed in all life cycle stages and
its expression attained maximum level in stationary
phase promastigotes, which are biochemically similar
to the infective metacyclic promastigotes. Starvation
condition, the trigger for metacyclogenesis in the
parasite, elevates LdPKAR1 expression and under
starvation condition promastigotes overexpressing
Ldpkar1 attained metacyclic features earlier than
normal cells. Furthermore, Ldpkar1 overexpression
accelerates autophagy, a starvation-induced cytological
event necessary for metacyclogenesis
and amastigote formation. Conditional silencing of
Ldpkar1 delays the induction of autophagy in the parasite.
The study, for the first time, reports the identification
of a functional cAMP-binding effector molecule from Leishmania that may modulate important cytological
events affecting metacyclogenesis
 
Publisher Blackwell Publishing
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1526/1/MOLECULAR_MICROBIOLOGY__83_(3)_548%2D564;2012[60].pdf
Bhattacharya, Arijit and Biswas, Arunima and Das, Pijush K (2012) Identification of a Protein Kinase A Regulatory Subunit from Leishmania having Importance in Metacyclogenesis Through Induction of Autophagy. Molecular Microbiology, 83 (3). pp. 548-564.
 
Relation http://dx.doi.org/10.1111/j.1365-2958.2011.07950.x
http://www.eprints.iicb.res.in/1526/