MAL decreases the internalization of the aquaporin-2 water channel

Erik Jan Kamsteeg, Amy S Duffield, Irene B M Konings, Joanna Spencer, Philipp Pagel, Peter M T Deen, Michael J. Caplan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16696-16701
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number42
DOIs
StatePublished - Oct 16 2007
Externally publishedYes

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Aquaporin 2
Aquaporins
Epithelial Cells
Kidney
Detergents
Membrane Proteins
Collecting Kidney Tubules
Body Water
Post Translational Protein Processing
Organelles
Serine
Transfection
Cultured Cells
Proteins
Homeostasis
Epithelium
Phosphorylation
Cell Membrane

Keywords

  • Epithelia
  • Sorting
  • Tetraspanin
  • Trafficking

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

MAL decreases the internalization of the aquaporin-2 water channel. / Kamsteeg, Erik Jan; Duffield, Amy S; Konings, Irene B M; Spencer, Joanna; Pagel, Philipp; Deen, Peter M T; Caplan, Michael J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 42, 16.10.2007, p. 16696-16701.

Research output: Contribution to journalArticle

Kamsteeg, Erik Jan ; Duffield, Amy S ; Konings, Irene B M ; Spencer, Joanna ; Pagel, Philipp ; Deen, Peter M T ; Caplan, Michael J. / MAL decreases the internalization of the aquaporin-2 water channel. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 42. pp. 16696-16701.
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