Tick Importin-α Is Implicated in the Interactome and Regulome of the Cofactor Subolesin

Pathogens

Alejandro Cabezas-Cruz¹  ArdM. Nijhof²  Sophia Pinecki Socias²  Nina Militzer²  Sara Artigas-Jerónimo³  José de la Fuente³  Margarita Villar³  Lesley Bell-Sakyi⁴  Grégory Caignard⁵  Damien Vitour⁵  Eleonore Allain⁵  Houssam Attoui⁵  Sandrine Lacour⁵  Jennifer Richardson⁵ 

[1] Anses, INRAE, Ecole Nationale Vétérinaire d’Alfort, UMR BIPAR, Laboratoire de Santé Animale, F-94700 Maisons-Alfort, France;Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany;SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo s/n, 13005 Ciudad Real, Spain;Tick Cell Biobank, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, 146 Brownlow Hill, Liverpool L3 5RF, UK;UMR 1161 Virologie, Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d’Alfort, Paris-Est Sup, 94700 Maisons-Alfort, France;

关键词: subolesin;    interactome;    regulome;    importin;    histone;    epigenetic;   

DOI  :  10.3390/pathogens10040457

来源: DOAJ

【 摘 要 】

Ticks and tick-borne diseases (TBDs) represent a burden for human and animal health worldwide. Currently, vaccines constitute the safest and most effective approach to control ticks and TBDs. Subolesin (SUB) has been identified as a vaccine antigen for the control of tick infestations and pathogen infection and transmission. The characterization of the molecular function of SUB and the identification of tick proteins interacting with SUB may provide the basis for the discovery of novel antigens and for the rational design of novel anti-tick vaccines. In the present study, we used the yeast two-hybrid system (Y2H) as an unbiased approach to identify tick SUB-interacting proteins in an Ixodes ricinus cDNA library, and studied the possible role of SUB as a chromatin remodeler through direct interaction with histones. The Y2H screening identified Importin-α as a potential SUB-interacting protein, which was confirmed in vitro in a protein pull-down assay. The sub gene expression levels in tick midgut and fat body were significantly higher in unfed than fed female ticks, however, the importin-α expression levels did not vary between unfed and fed ticks but tended to be higher in the ovary when compared to those in other organs. The effect of importin-α RNAi was characterized in I. ricinus under artificial feeding conditions. Both sub and importin-α gene knockdown was observed in all tick tissues and, while tick weight was significantly lower in sub RNAi-treated ticks than in controls, importin-α RNAi did not affect tick feeding or oviposition, suggesting that SUB is able to exert its function in the absence of Importin-α. Furthermore, SUB was shown to physically interact with histone 4, which was corroborated by protein pull-down and western blot analysis. These results confirm that by interacting with numerous tick proteins, SUB is a key cofactor of the tick interactome and regulome. Further studies are needed to elucidate the nature of the SUB-Importin-α interaction and the biological processes and functional implications that this interaction may have.

【 授权许可】

Unknown