Theileria highjacks JNK2 into a complex with the macroschizont GPI (GlycosylPhosphatidylInositol)‐anchored surface protein p104. (5th December 2018)

• Record Type: Journal Article
• Authors: Latré De Laté, Perle; Haidar, Malak; Ansari, Hifzur; Tajeri, Shahin; Szarka, Eszter; Alexa, Anita; Woods, Kerry; Reményi, Attila; Pain, Arnab; Langsley, Gordon
• Is Part Of: Cellular microbiology. Volume 21:Number 3(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-12-05
• Subjects: Dissemination -- JNK2 -- penetrating peptide -- PKA -- Theileria; Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12973
• Languages: English
• ISSNs: 1462-5814

Abstract

Abstract: Constitutive c‐Jun N‐terminal kinase (JNK) activity characterizes bovine T and B cells infected with Theileria parva, and B cells and macrophages infected with Theileria 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‐(GlycosylPhosphatidylInositol)‐anchor T. annulata plasma membrane protein. Sequestration of JNK2 depended on Protein Kinase‐A (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.