A conserved retromer-independent function for RAB-6.2/RAB6 in C. elegans epidermis integrity

Abstract

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