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lüll An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes Benfenati V; Caprini M; Dovizio M; Mylonakou MN; Ferroni S; Ottersen OP; Amiry-Moghaddam MProc Natl Acad Sci U S A 2011[Feb]; 108 (6): 2563-8Regulatory 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 Ca(2+) and RVD. Coimmunoprecipitation and immunohistochemistry analyses show that AQP4 and TRPV4 interact and colocalize. Functional analysis of an astrocyte-derived cell line expressing TRPV4 but not AQP4 shows that RVD and intracellular Ca(2+) 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.|*Cell Size[MESH]|Animals[MESH]|Aquaporin 1/genetics/metabolism[MESH]|Aquaporin 4/genetics/*metabolism[MESH]|Astrocytes/cytology/*metabolism[MESH]|COS Cells[MESH]|Calcium/metabolism[MESH]|Chlorocebus aethiops[MESH]|Cricetinae[MESH]|Humans[MESH]|Mice[MESH]|Mice, Knockout[MESH]|Osmotic Pressure/physiology[MESH]|Signal Transduction/physiology[MESH]|TRPV Cation Channels/genetics/*metabolism[MESH] |