Two Very Long Chain Fatty Acid Acyl-CoA Synthetase Genes, acs-20 and acs-22, Have Roles in the Cuticle Surface Barrier in Caenorhabditis elegans

Abstract

In multicellular organisms, the surface barrier is essential for maintaining the internal environment. In mammals, the barrier is the stratum corneum. Fatty acid transport protein 4 (FATP4) is a key factor involved in forming the stratum corneum barrier. Mice lacking Fatp4 display early neonatal lethality with features such as tight, thick, and shiny skin, and a defective skin barrier. These symptoms are strikingly similar to those of a human skin disease called restrictive dermopathy. FATP4 is a member of the FATP family that possesses acyl-CoA synthetase activity for very long chain fatty acids. How Fatp4 contributes to skin barrier function, however, remains to be elucidated. In the present study, we characterized two Caenorhabditis elegans genes, acs-20 and acs-22, that are homologous to mammalian FATPs. Animals with mutant acs-20 exhibited defects in the cuticle barrier, which normally prevents the penetration of small molecules. acs-20 mutant animals also exhibited abnormalities in the cuticle structure, but not in epidermal cell fate or cell integrity. The acs-22 mutants rarely showed a barrier defect, whereas acs-20;acs-22 double mutants had severely disrupted barrier function. Moreover, the barrier defects of acs-20 and acs-20;acs-22 mutants were rescued by acs-20, acs-22, or human Fatp4 transgenes. We further demonstrated that the incorporation of exogenous very long chain fatty acids into sphingomyelin was reduced in acs-20 and acs-22 mutants. These findings indicate that C. elegans Fatp4 homologue(s) have a crucial role in the surface barrier function and this model might be useful for studying the fundamental molecular mechanisms underlying human skin barrier and relevant diseases.

Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans

“…The C. elegans genome contains 22 genes known to encode acyl-CoA synthetase/fatty acid transporter (Zhang et al 2013), of which ACS-20 is required for incorporation of exogenous very long chain fatty acids into sphingomyelin (Kage-Nakadai et al 2010). While ACS-22 may functionally overlap with ACS-20 (Kage-Nakadai et al 2010), we found that only ACS-20 is required for the increased fat accumulation under iron overload, suggesting that ACS-20, like SGK-1, regulates lipid hemostasis under iron overload.…”

Proteomic Study and Marker Protein Identification of Caenorhabditis elegans Lipid Droplets

“…Of particular interest are the acyl-CoA synthetase (ACS) family, the homologue of mammalian adipose triglyceride lipase ATGL-1, and the short chain fatty acid dehydrogenases (DHS) family. C. elegans ACS-20 and ACS-22 are implicated in the incorporation of very long chain fatty acids into sphingomyelin, which may be linked to cuticle barrier formation (30). DHS-28, a peroxisomal dehydrogenase, has been shown to regulate long chain fatty acid ␤-oxidation and LD size (21).…”

A potential role for fatty acid biosynthesis genes during molting and cuticle formation in Caenorhabditis elegans

“…S3). Furthermore, Kage-Nakadai (25) reported that very long chain fatty acyl-CoA synthetase plays an important role in the cuticle surface barrier. As both POD-2 and FASN-1 contribute to the biosynthesis of MUFA and polyunsaturated fatty acids in C. elegans (26), it would be reasonable to predict that RNAi against pod-2 and fasn-1 would affect cuticle integrity.…”