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The ADP ribosylation factor (ARF) GTPase activation protein ASAP1 possesses multiple biological functions, including regulation of cytoskeletal dynamics, small GTP-binding protein receptor recycling, and intracellular vesicle trafficking. Recently,  ASAP1  polymorphisms have been reported to be associated with human susceptibility to tuberculosis (TB) according to a large-scale genome-wide association study (GWAS); ASAP1 expression affects dendritic cell migration, which may be involved in TB predisposition. However, it remains unclear whether ASAP1 affects TB  in vivo . To address this issue, we used zebrafish as a model system to examine the effects of Asap1 against  Mycobacterium marinum , an organism closely related to  Mycobacterium tuberculosis . Two zebrafish  asap1  homologs ( asap1a and asap1b ) were identified and characterized. By morpholino knockdown of  asap1a  and  asap1b  as a whole, we found that the  asap1  morphants showed a higher mycobacterial load than the controls, which was almost rescued by injecting  asap1  mRNA that confers resistance to mycobacterial infection. These Asap1-depleted zebrafish also exhibited decreased macrophage migration in response to tail injury or upon infection with  M. marinum  in the hindbrain ventricle, which was also proved in THP1-derived macrophages of knockdown ASAP1. Together, these findings represent a new perspective on the role of Asap1 in resistance to mycobacterial infection.

Asap1 Affects the Susceptibility of Zebrafish to Mycobacterium by Regulating Macrophage Migration