Unknown

Dataset Information

0

Small GTPase Rab14 down-regulates UT-A1 urea transport activity through enhanced clathrin-dependent endocytosis.


ABSTRACT: The UT-A1 urea transporter plays an important role in the urinary concentration mechanism. However, the molecular mechanisms regarding UT-A1 trafficking, endocytosis, and degradation are still unclear. In this study, we identified the small GTPase Rab14 as a binding partner to the C terminus of UT-A1 in a yeast 2-hybrid assay. Interestingly, UT-A1 binding is preferential for the GDP-bound inactive form of Rab14. Coinjection of Rab14 in Xenopus oocytes results in a decrease of UT-A1 urea transport activity, suggesting that Rab14 acts as a negative regulator of UT-A1. We subsequently found that Rab14 reduces the cell membrane expression of UT-A1, as evidenced by cell surface biotinylation. This effect is blocked by chlorpromazine, an inhibitor of the clathrin-mediated endocytic pathway, but not by filipin, an inhibitor of the caveolin-mediated endocytic pathway. In kidney, Rab14 is mainly expressed in IMCD epithelial cells with a pattern identical to UT-A1 expression. Consistent with its role in participating in clathrin-mediated endocytosis, Rab14 localizes in nonlipid raft microdomains and codistributes with Rab5, a marker of the clathrin-mediated endocytic pathway. Taken together, our study suggests that Rab14, as a novel UT-A1 partner, may have an important regulatory function for UT-A1 urea transport activity in the kidney inner medulla.

SUBMITTER: Su H 

PROVIDER: S-EPMC4046183 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4378103 | BioStudies
2003-01-01 | S-EPMC149460 | BioStudies
2015-01-01 | S-EPMC4490382 | BioStudies
1000-01-01 | S-EPMC2889632 | BioStudies
2013-01-01 | S-EPMC3890325 | BioStudies
2004-01-01 | S-EPMC409942 | BioStudies
1969-12-31 | S-SCDT-EMBOJ-2018-100116 | BioStudies
2019-01-01 | S-EPMC6396150 | BioStudies
2015-01-01 | S-EPMC4353700 | BioStudies
2015-01-01 | S-EPMC4501499 | BioStudies