期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 6, 页码 2563-2568出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1012867108
关键词
water channel; glia; brain edema
资金
- Research Council of Norway
- European Molecular Biology Organization [ASTF89-2007]
- University of Bologna
- Progetti Strategici di Ateneo
- EU [PF6 035859-2, FP7-ICT-248052]
- Italian Minister for University [FIRBRBPR05JH2]
Regulatory volume decrease (RVD) is a key mechanism for volume control that serves to prevent detrimental swelling in response to hypo-osmotic stress. The molecular basis of RVD is not understood. Here we show that a complex containing aquaporin-4 (AQP4) and transient receptor potential vanilloid 4 (TRPV4) is essential for RVD in astrocytes. Astrocytes from AQP4-KO mice and astrocytes treated with TRPV4 siRNA fail to respond to hypotonic stress by increased intracellular Ca2+ and RVD. Coimmunoprecipitation and immunohistochemistry analyses showthat AQP4 and TRPV4 interact and colocalize. Functional analysis of an astrocyte-derived cell line expressing TRPV4 but not AQP4 shows that RVD and intracellular Ca2+ response can be reconstituted by transfection with AQP4 but not with aquaporin-1. Our data indicate that astrocytes contain a TRPV4/AQP4 complex that constitutes a key element in the brain's volume homeostasis by acting as an osmosensor that couples osmotic stress to downstream signaling cascades.
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