A conserved retromer-independent function for RAB-6.2/RAB6 inC. elegansepidermis 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 proteins. 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 expression of a mouse RAB6A cDNA can rescue defects in C. elegans 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 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 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.

Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0

“…2(ok2254) culture plates during normal maintenance, a phenotype very rarely observed in wild-type cultures…. We hypothesized that RAB-6.2 is required for skin integrity’ [ 170 ].…”

Dynein directs prophase centrosome migration to control the stem cell division axis in the developingC. elegansepidermis

“…Dynein–driven membrane trafficking may also be required for proper secretion of cuticle components. Consistent with this possibility, a null mutant of the small GTPase RAB-6.2, which marks golgi-derived exocytotic vesicles that have been identified as dynein cargo in other species, exhibits cuticle integrity defects (Kim et al ., 2019). It will be interesting to investigate these potential contributions of dynein to epidermal development in future work.…”

Six Biomarkers Expressed Stably in Urinary Exosomes During All Life Stages - As the Reference Markers in Urinary Quantification

“…Although the speci c molecular role of Rab GTPases in the development process is still unclear, many studies have emphasized the necessity of Rab GTPases in the development of multiple mammalian embryos [25]. In multiple experiments, the mice that knocked out the Rab proteins died at the embryonic stage or shortly after birth [26][27][28][29]. The above shows that Rab GTPases play an essential and indispensable role in embryonic development.…”