4.8 Article

MAL decreases the internalization of the aquaporin-2 water channel

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0708023104

Keywords

epithelia; sorting; tetraspanin; trafficking

Funding

  1. NIDDK NIH HHS [P01 DK017433, DK17433] Funding Source: Medline
  2. NIGMS NIH HHS [R01 GM072614, GM072614] Funding Source: Medline

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Body water homeostasis depends critically on the hormonally regulated trafficking of aquaporin-2 (AQP2) water channels in renal collecting duct epithelial cells. Several types of posttranslational modifications are clearly involved in controlling the distribution of AQP2 between intracellular vesicles and the apical plasma membrane. Little is known, however, about the protein interactions that govern the trafficking of AQP2 between these organelles. MAL is a detergent-resistant membrane-associated protein implicated in apical sorting events. We wondered, therefore, whether MAL plays a role in the regulated trafficking of AQP2 between intracellular vesicles and the apical surface. We find that AQP2 and MAL are coexpressed in epithelial cells of the kidney collecting duct. These two proteins interact, both in the native kidney and when expressed by transfection in cultured cells. The S256-phosphorylated form of AQP2 appears to interact more extensively with MAL than does the water channel protein not phosphorylated at this serine. We find that MAL is not involved in detergent-resistant membrane association or apical delivery of AQP2 in LLC-PK1 renal epithelial cells. Instead, MAL increases the S256 phosphorylation and apical surface expression of AQP2. Furthermore, internalization experiments show that MAL induces surface expression of AQP2 by attenuating its internalization. Thus, the involvement of MAL in the cell surface retention of apical membrane proteins could play an important role in regulated absorption and secretion in transporting epithelia.

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