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

Latré De Laté, Perle; Haidar, Malak; Ansari, Hifzur; Tajeri, Shahin; Szarka, Eszter; Alexa, Anita; Woods, Kerry; Reményi, Attila; Pain, Arnab; Langsley, Gordon (2019). Theileria highjacks JNK2 into a complex with the macroschizont GPI (GlycosylPhosphatidylInositol)-anchored surface protein p104. Cellular microbiology, 21(3), e12973. Wiley 10.1111/cmi.12973

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology

UniBE Contributor:

Woods, Kerry

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 630 Agriculture

ISSN:

1462-5822

Publisher:

Wiley

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

11 Mar 2020 13:00

Last Modified:

11 Mar 2020 13:00

Publisher DOI:

10.1111/cmi.12973

PubMed ID:

30412643

Uncontrolled Keywords:

Dissemination JNK2 PKA Theileria penetrating peptide

BORIS DOI:

10.7892/boris.140643

URI:

https://boris.unibe.ch/id/eprint/140643

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