Akirin/Subolesin regulatory mechanisms at host/tick-pathogen interactions

Abstract

Ticks and tick-borne pathogens such as Anaplasma phagocytophilum affect human and animal health worldwide and thus the characterization of host/tick-pathogen interactions is important for the control of tick-borne diseases. The vertebrate regulatory proteins Akirins and its tick ortholog, Subolesin, are conserved throughout the metazoan and involved in the regulation of different biological processes such as immune response to pathogen infection. Akirin/Subolesin have a key role in host/tick-pathogen interactions and exert its regulatory function primarily through interacting proteins such as transcription factors, chromatin remodelers and RNA-associated proteins. Recent results have provided evidence of akirin/subolesin genetic interactions and the interaction of Akirin/Subolesin with histones, thus suggesting a role in direct chromatin remodeling. Finally, and still to be proven, some models suggest the possibility of direct Akirin/Subolesin protein interactions with DNA. Future research should advance the characterization of Akirin/Subolesin interactome and its functional role at the host/tick-pathogen interface. These results have implications for translational biotechnology and medicine for the development of new effective interventions for the control of ticks and tick-borne diseases.

Keywords: Akirin; Subolesin; chromatin; epigenetics; histone; host; immune response; regulome; tick.

Figure 1.

Gene expression in response to Akirin/Subolesin and A. phagocytophilum infection. The results support the impact of pathogen infection and akirin2/subolesin knockout/knockdown on gene expression in human HL60 and tick ISE6 cells. The piece at central panel (Roberto Alvarez Ríos, Origin 3, oil on canvas, 1962, courtesy of KGJ Collection, Ciudad Real, Spain) illustrates the origin and conserved role of Akirin/Subolesin in metazoa.

Figure 2.

Akirin/Subolesin interactions to regulate gene expression. The results support the Akirin/Subolesin interactions with chromatin remodelers, transcription factors, histones for direct chromatin remodeling and other regulatory proteins such as importins, histone modifying enzymes and RNA-associated proteins. Preliminary evidence of akirin/subolesin genetic interactions have been provided and still to be proven (question mark); protein models suggest the possibility of direct Akirin/Subolesin protein interactions with DNA. The piece at central panel (Gustavo Pérez Monzón, untitled, mixed media on cardboard, ca. 1980, courtesy of KGJ Collection, Ciudad Real, Spain) illustrates the complex regulatory interaction networks of Akirin/Subolesin.