4.7 Article

Reciprocal interaction with G-actin and tropomyosin is essential for aquaporin-2 trafficking

Journal

JOURNAL OF CELL BIOLOGY
Volume 182, Issue 3, Pages 587-601

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200709177

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Funding

  1. Japan Society for the Promotion of Science
  2. Japan Ministry of Education, Culture, Sports, Science and Technology
  3. Grants-in-Aid for Scientific Research [19058001] Funding Source: KAKEN

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Trafficking of water channel aquaporin-2 (AQP2) to the apical membrane and its vasopressin and protein kinase A (PKA)-dependent regulation in renal collecting ducts is critical for body water homeostasis. We previously identified an AQP2 binding protein complex including actin and tropomyosin-5b (TM5b). We show that dynamic interactions between AQP2 and the actin cytoskeleton are critical for initiating AQP2 apical targeting. Specific binding of AQP2 to G-actin in reconstituted liposomes is negatively regulated by PKA phosphorylation. Dual color fluorescence cross-correlation spectroscopy reveals local AQP2 interaction with G-actin in live epithelial cells at single-molecule resolution. Cyclic adenosine monophosphate signaling and AQP2 phosphorylation release AQP2 from G-actin. In turn, AQP2 phosphorylation increases its affinity to TM5b, resulting in reduction of TM5b bound to F-actin, subsequently inducing F-actin destabilization. RNA interference-mediated knockdown and overexpression of TM5b confirm its inhibitory role in apical trafficking of AQP2. These findings indicate a novel mechanism of channel protein trafficking, in which the channel protein itself critically regulates local actin reorganization to initiate its movement.

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