Beschreibung:
Abstract: Serum- and glucocorticoid-inducible protein kinase (SGK) in vertebrates play a role during development and in pathophysiology of several diseases by regulating the abundance and activity of several ion channels, glucose uptake, cell cycle progression, and death. In Caenorhabditis elegans (C. elegans), the single sgk-1 gene product has been shown to mediate DAF-2/insulin-like signaling, TRPA-1 cold sensing channel and target of rapamycin complex 2 (TORC2) to regulate longevity, stress response, development, and lipid metabolism. In this study, I identified and characterized a novel function of C. elegans SGK-1 in endomembrane trafficking (EMT).<br>Transgenic expression of sgk-1 results in the generation of vacuole like structures (VLSs) in the intestine which resemble the endosomal phenotype displayed in either rab-10 or rme-1 mutants. The endocytic transport of candidated membrane receptors are blocked in the VLSs which also harbor aberrant phospholipid content. The costaining analysis revealed that VLSs are enlarged endosomes, since they are predominantly labeled by GFP::RAB-5/LMP-1::GFP. <br>Bioinformatic analysis predicted that SGK-1 contains a conserved Phox homology (PX) domain. Mutation either in the PX or the kinase domain of SGK-1 suppress the generation of VLSs in sgk-1 transgene. Additionally, deletion of sgk-1 suppresses the formation of VLSs in rab-10 or rme-1 mutants, further supporting a role of SGK-1 in endocytic trafficking. Besides, the sgk-1 mutant contains greatly increased numbers of lysosome-related organelles (LROs) which were suggested to be primarily derived from endosomes, indicating a disrupted function of the endosome in the sgk-1 mutant. Epistatic analysis for the upstream regulators of SGK-1 based on the VLSs phenotype in sgk-1 transgenic and rab-10 mutant animals indicate that the endosomal function of SGK-1 is mainly controlled by TORC2. In summary, C. elegans SGK-1 localizes to endosomes in the conserved TORC2 pathway to regulate the basolateral endocytic trafficking in the intestine