Theileria\n highjacks JNK2 into a complex with the macroschizont GPI-anchored surface protein p104
Type
ArticleAuthors
de Laté, Perle LatréHaidar, Malak
Ansari, Hifzur Rahman

Tajeri, Shahin
Szarka, Eszter
Alexa, Anita
Woods, Kerry

Reményi, Attila
Pain, Arnab

Langsley, Gordon

KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionComputational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Bioscience Program
Pathogen Genomics Laboratory
KAUST Grant Number
URF/1/2610-01-01BAS/1/1020-01-01
URF/1/2610-01-01
Date
2018-12-05Permanent link to this record
http://hdl.handle.net/10754/629855
Metadata
Show full item recordAbstract
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.Citation
De Laté PL, Haidar M, Ansari H, Tajeri S, Szarka E, et al. (2018) Theileria\n highjacks JNK2 into a complex with the macroschizont GPI-anchored surface protein p104. Cellular Microbiology: e12973. Available: http://dx.doi.org/10.1111/cmi.12973.Sponsors
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.Publisher
WileyJournal
Cellular MicrobiologyAdditional Links
https://onlinelibrary.wiley.com/doi/abs/10.1111/cmi.12973ae974a485f413a2113503eed53cd6c53
10.1111/cmi.12973