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

Perle Latré de Laté, Malak Haidar, Hifzur Rahman Ansari, Shahin Tajeri, Eszter Szarka, Anita Alexa, Kerry Woods, Attila Reményi, Arnab Pain, Gordon Langsley

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)e12973
JournalCellular Microbiology
Volume21
Issue number3
DOIs
StatePublished - Dec 5 2018

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): URF/1/2610-01-01, BAS/1/1020-01-01, URF/1/2610-01-01
Acknowledgements: We would like to thank Professor Brian Shiels for gift of antibodies to Theileria p104 (mAb 1C12). This work was supported by the grant Labex ParaFrap [ANR-11-LABX-0024] and core funding from INSERM and the CNRS awarded to GL and a CRG4 grant [URF/1/2610-01-01] from the Office for Sponsored Research (OSR) in King Abdullah University of Science and Technology (KAUST) award to AP and GL and the faculty baseline fund (BAS/1/1020-01-01) awarded to AP. AR acknowledges a Hungarian NKFIH grant NN114309. KW ackowledges Swiss National Science Foundation (SNF) Grant number PZ00P3_154689. PLdL and ST were recipients of ParaFrap post-doctoral fellowships and MH and HRH were supported by the URF/1/2610-01-01 grant from KAUST. There are no competing financial interests in relation to the work described.

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