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Theileria highjacks JNK2 into a complex with the macroschizont GPI-anchored surface protein p104.

De Laté, Perle Latré and Haidar, Malak and Ansari, Hifzur and Tajeri, Shahin and Szarka, Eszter and Alexa, Anita and Reményi, Attila (2019) Theileria highjacks JNK2 into a complex with the macroschizont GPI-anchored surface protein p104. CELLULAR MICROBIOLOGY, 21 (3). ISSN 1462-5814

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Abstract

Constitutive JNK activity characterizes bovine T and B cells infected with Theileria parva, and B cells and macrophages infected with T. annulata. Here, we show that T. annulata infection of macrophages manipulates JNK activation by recruiting JNK2 and not JNK1 to the parasite surface, whereas JNK1 is found predominantly in the host cell nucleus. At the parasite's surface JNK2 forms a complex with p104 a GPI-anchored T. annulata plasma membrane protein. Sequestration of JNK2 depended on PKA-mediated phosphorylation of a JNK-binding motif common to T. parva and a cell penetrating peptide harbouring the conserved p104 JNK-binding motif competitively ablated binding, whereupon liberated JNK2 became ubiquitinated and degraded. Cytosolic sequestration of JNK2 suppressed small mitochondrial ARF-mediated autophagy, whereas it sustained nuclear JNK1 levels, c-Jun phosphorylation and matrigel traversal. Therefore, T. annulata sequestration of JNK2 contributes to both survival and dissemination of Theileria-transformed macrophages.

Item Type: Article
Additional Information: Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, 75014, France Inserm U1016, CNRS UMR8104, Cochin Institute, Paris, France Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Jeddah 23955-6900, Saudi Arabia Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary Vetsuisse Faculty, University of Bern, Bern, Switzerland Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan Export Date: 20 December 2018 Article in Press CODEN: CEMIF Correspondence Address: Langsley, G.; Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris CitéFrance; email: gordon.langsley@inserm.fr
Uncontrolled Keywords: DISSEMINATION; pKa; JNK2; penetrating peptide; Theileria;
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 05 Mar 2019 15:17
Last Modified: 05 Mar 2019 15:17
URI: http://real.mtak.hu/id/eprint/91799

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