In:
Molecular Microbiology, Wiley, Vol. 87, No. 6 ( 2013-03), p. 1133-1150
Abstract:
In animals, inositol 1,4,5‐trisphosphate receptors ( IP 3 Rs ) are ion channels that play a pivotal role in many biological processes by mediating Ca 2+ release from the endoplasmic reticulum. Here, we report the identification and characterization of a novel IP 3 R in the parasitic protist, T rypanosoma cruzi , the pathogen responsible for C hagas disease. DT 40 cells lacking endogenous IP 3 R genes expressing T . cruzi IP 3 R ( TcIP 3 R ) exhibited IP 3 ‐mediated Ca 2+ release from the ER , and demonstrated receptor binding to IP 3 . TcIP 3 R was expressed throughout the parasite life cycle but the expression level was much lower in bloodstream trypomastigotes than in intracellular amastigotes or epimastigotes. Disruption of two of the three TcIP 3 R gene loci led to the death of the parasite, suggesting that IP 3 R is essential for T . cruzi . Parasites expressing reduced or increased levels of TcIP 3 R displayed defects in growth, transformation and infectivity, indicating that TcIP 3 R is an important regulator of the parasite's life cycle. Furthermore, mice infected with T . cruzi expressing reduced levels of TcIP 3 R exhibited a reduction of disease symptoms, indicating that TcIP 3 R is an important virulence factor. Combined with the fact that the primary structure of TcIP 3 R has low similarity to that of mammalian IP 3 Rs , TcIP 3 R is a promising drug target for C hagas disease.
Type of Medium:
Online Resource
ISSN:
0950-382X
,
1365-2958
DOI:
10.1111/mmi.2013.87.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
1501537-3
detail.hit.zdb_id:
619315-8
