Rab7 involves Vps35 to mediate AQP2 sorting and apical trafficking in collecting duct cells
| Autor: | Wei-Ling Wang, Chan-Wei Yang, Chin-Fu Liu, Ming-Jiun Yu, Kit Yee Wong, Shih-Han Su |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Vasopressin Time Factors Retromer Physiology Endosome Vasopressins Vesicular Transport Proteins Endosomes urologic and male genital diseases 03 medical and health sciences VPS35 Mice 0302 clinical medicine Animals Humans Kidney Tubules Collecting Vacuolar protein sorting Aquaporin 2 urogenital system Chemistry Lysosome-Associated Membrane Glycoproteins rab7 GTP-Binding Proteins Apical membrane Cell biology Retromer complex Protein Transport 030104 developmental biology HEK293 Cells rab GTP-Binding Proteins 030220 oncology & carcinogenesis Proteolysis hormones hormone substitutes and hormone antagonists |
| Zdroj: | American journal of physiology. Renal physiology. 318(4) |
| ISSN: | 1522-1466 |
| Popis: | Aquaporin-2 (AQP2) is a vasopressin-regulated water channel protein responsible for osmotic water reabsorption by kidney collecting ducts. In response to vasopressin, AQP2 traffics from intracellular vesicles to the apical plasma membrane of collecting duct principal cells, where it increases water permeability and, hence, water reabsorption. Despite continuing efforts, gaps remain in our knowledge of vasopressin-regulated AQP2 trafficking. Here, we studied the functions of two retromer complex proteins, small GTPase Rab7 and vacuolar protein sorting 35 (Vps35), in vasopressin-induced AQP2 trafficking in a collecting duct cell model (mpkCCD cells). We showed that upon vasopressin removal, apical AQP2 returned to Rab5-positive early endosomes before joining Rab11-positive recycling endosomes. In response to vasopressin, Rab11-associated AQP2 trafficked to the apical plasma membrane before Rab5-associated AQP2 did so. Rab7 knockdown resulted in AQP2 accumulation in early endosomes and impaired vasopressin-induced apical AQP2 trafficking. In response to vasopressin, Rab7 transiently colocalized with Rab5, indicative of a role of Rab7 in AQP2 sorting in early endosomes before trafficking to the apical membrane. Rab7-mediated apical AQP2 trafficking in response to vasopressin required GTPase activity. When Vps35 was knocked down, AQP2 accumulated in recycling endosomes under vehicle conditions and did not traffic to the apical plasma membrane in response to vasopressin. We conclude that Rab7 and Vps35 participate in AQP2 sorting in early endosomes under vehicle conditions and apical membrane trafficking in response to vasopressin. |
| Databáze: | OpenAIRE |
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