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Aquaporin clears its own path

When TM5b is knocked down (right), aquaporin (green) can reach the membrane even without phosphorylation. Lines show position of cross-sections shown in bottom panels.

Aquaporin takes charge of getting itself to the membrane, say Noda et al.

In the renal collecting duct, aquaporin channels increase permeability and are central to water homeostasis. The channel normally hangs out in the cytoplasm, but when the body needs to retain water, it relocates to the apical membrane, allowing water to flow from the tubule into the cell.

This relocation is under the control of antidiuretic hormone. The hormone activates protein kinase A (PKA), which in turn phosphorylates aquaporin. But once phosphorylated, how does aquaporin relocate? The only clue was the authors' previous study showing aquaporin can bind both actin and tropomyosin (TM5b).

Phosphorylation, the team found, dissociated aquaporin from G-actin molecules, but also destabilized F-actin. They speculated that this destabilization might be related to aquaporin's ability to bind TM5b, because TM5b is a known F-actin stabilizer.

Overexpression of TM5b indeed increased the amount of F-actin and prevented aquaporin from reaching the membrane. The authors thus propose a model whereby, upon phosphorylation, aquaporin detaches from G-actin and binds to TM5b, causing TM5b to lose its grip on F-actin. The F-actin then depolymerizes, opening the way for aquaporin to reach the membrane.

Because trafficking of numerous other channels is regulated by phosphorylation, and because channel–actin interactions have also been found elsewhere, Noda suggests that other channels may also promote their own relocation through this scheme. She also suggests TM5b may be an appropriate therapeutic target for diabetes insipidus, in which aquaporin's ability to reach the membrane is impaired.

Noda, Y., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200709177.[Abstract/Free Full Text]

Richard Robinson

rrobinson{at}nasw.org

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This Article Full Text (PDF, 1218K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                            What's this?