Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii.
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009325 |
| _version_ | 1819020401103077376 |
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| author | Priyanka Bansal Neelam Antil Manish Kumar Yoshiki Yamaryo-Botté Rahul Singh Rawat Sneha Pinto Keshava K Datta Nicholas J Katris Cyrille Y Botté T S Keshava Prasad Pushkar Sharma |
| author_facet | Priyanka Bansal Neelam Antil Manish Kumar Yoshiki Yamaryo-Botté Rahul Singh Rawat Sneha Pinto Keshava K Datta Nicholas J Katris Cyrille Y Botté T S Keshava Prasad Pushkar Sharma |
| author_sort | Priyanka Bansal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T03:50:37Z |
| format | Article |
| id | doaj.art-979e8f930049401d96d1e51cd7e04e30 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T03:50:37Z |
| publishDate | 2021-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-979e8f930049401d96d1e51cd7e04e302022-12-21T19:16:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-02-01172e100932510.1371/journal.ppat.1009325Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii.Priyanka BansalNeelam AntilManish KumarYoshiki Yamaryo-BottéRahul Singh RawatSneha PintoKeshava K DattaNicholas J KatrisCyrille Y BottéT S Keshava PrasadPushkar SharmaApicomplexan 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.https://doi.org/10.1371/journal.ppat.1009325 |
| spellingShingle | Priyanka Bansal Neelam Antil Manish Kumar Yoshiki Yamaryo-Botté Rahul Singh Rawat Sneha Pinto Keshava K Datta Nicholas J Katris Cyrille Y Botté T S Keshava Prasad Pushkar Sharma Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii. PLoS Pathogens |
| title | Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii. |
| title_full | Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii. |
| title_fullStr | Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii. |
| title_full_unstemmed | Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii. |
| title_short | Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii. |
| title_sort | protein kinase tgcdpk7 regulates vesicular trafficking and phospholipid synthesis in toxoplasma gondii |
| url | https://doi.org/10.1371/journal.ppat.1009325 |
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