A conserved retromer-independent function for RAB-6.2 in C. elegans epidermis integrity

Rab proteins are conserved small GTPases that coordinate intracellular trafficking essential to cellular function and homeostasis. RAB-6.2 is a highly conserved ortholog of human RAB6 proteins. RAB-6.2 is expressed in most tissues in and is known to function in neurons and in the intestine to mediate retrograde trafficking. Here, we show that RAB-6.2 is necessary for cuticle integrity and impermeability in RAB-6.2 functions in the epidermis to instruct skin integrity. Significantly, we show that expression of a mouse RAB6A cDNA can rescue defects in epidermis caused by lack of RAB-6.2, suggesting functional conservation across phyla. We also show that the novel function of RAB-6.2 in cuticle development is distinct from its previously described function in neurons. Exocyst mutants partially phenocopy -null animals, and null animals phenocopy mutants that have defective surface glycosylation. These results suggest that RAB-6.2 may mediate the trafficking of one or many secreted glycosylated cuticle proteins directly, or might act indirectly by trafficking glycosylation enzymes to their correct intracellular localization.