Very long chain fatty acid (VLCFA) is activated by VLCFA acyl-CoA synthetase (ACSVL) to be degraded or incorporated into a variety of lipids such as glycerolipids, phospholipids, and sphingolipids. In mammals, ACSVL family is composed of six members called fatty acid transport proteins (FATPs) that differ in their tissue expression patterns and physiological roles. In C. elegans, two genes
acs-20 (F28D1.9) and
acs-22 (D1009.1), which are highly homologous to ACSVL family, are found in the genome. However, their activities and physiological roles are poorly understood, so far. In this study, we found that the knockout mutant of
acs-20 is defective in the cuticle barrier that prevents penetration of small molecules.
acs-22 mutant alone rarely exhibits the barrier defect, but
acs-20;
acs-22 double mutant shows a severely disrupted barrier function. Moreover, the phenotypes of
acs-20 and
acs-20;
acs-22 mutants are rescued by
acs-20,
acs-22 or human FATP4 transgenes. Finally, we show that the mutants of
acs-20 and
acs-22 show reduced incorporation of exogenous VLCFA into sphingomyelin in living worms. These results indicate that ACS-20 and ACS-22 are ACSVLs playing roles in the barrier function in C.elegans.