In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 2 ( 2021-2-26), p. e1009325-
Abstract:
Apicomplexan parasites are causative agents of major human diseases. Calcium Dependent Protein Kinases (CDPKs) are crucial components for the intracellular development of apicomplexan parasites and are thus considered attractive drug targets. CDPK7 is an atypical member of this family, which initial characterization suggested to be critical for intracellular development of both Apicomplexa Plasmodium falciparum and Toxoplasma gondii . However, the mechanisms via which it regulates parasite replication have remained unknown. We performed quantitative phosphoproteomics of T . gondii lacking TgCDPK7 to identify its parasitic targets. Our analysis lead to the identification of several putative TgCDPK7 substrates implicated in critical processes like phospholipid (PL) synthesis and vesicular trafficking. Strikingly, phosphorylation of TgRab11a via TgCDPK7 was critical for parasite intracellular development and protein trafficking. Lipidomic analysis combined with biochemical and cellular studies confirmed that TgCDPK7 regulates phosphatidylethanolamine (PE) levels in T . gondii . These studies provide novel insights into the regulation of these processes that are critical for parasite development by TgCDPK7.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009325
DOI:
10.1371/journal.ppat.1009325.g001
DOI:
10.1371/journal.ppat.1009325.g002
DOI:
10.1371/journal.ppat.1009325.g003
DOI:
10.1371/journal.ppat.1009325.g004
DOI:
10.1371/journal.ppat.1009325.g005
DOI:
10.1371/journal.ppat.1009325.g006
DOI:
10.1371/journal.ppat.1009325.g007
DOI:
10.1371/journal.ppat.1009325.s001
DOI:
10.1371/journal.ppat.1009325.s002
DOI:
10.1371/journal.ppat.1009325.s003
DOI:
10.1371/journal.ppat.1009325.s004
DOI:
10.1371/journal.ppat.1009325.s005
DOI:
10.1371/journal.ppat.1009325.s006
DOI:
10.1371/journal.ppat.1009325.s007
DOI:
10.1371/journal.ppat.1009325.s008
DOI:
10.1371/journal.ppat.1009325.s009
DOI:
10.1371/journal.ppat.1009325.s010
DOI:
10.1371/journal.ppat.1009325.s011
DOI:
10.1371/journal.ppat.1009325.s012
DOI:
10.1371/journal.ppat.1009325.s013
DOI:
10.1371/journal.ppat.1009325.s014
DOI:
10.1371/journal.ppat.1009325.s015
DOI:
10.1371/journal.ppat.1009325.s016
DOI:
10.1371/journal.ppat.1009325.s017
DOI:
10.1371/journal.ppat.1009325.s018
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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