An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes.
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 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.
Institute for Nanostructured Materials, Consiglio Nazionale delle Ricerche, 40129 Bologna, Italy.
Valentina
V
Benfenati
Marco
M
Caprini
Melania
M
Dovizio
Maria N
MN
Mylonakou
Stefano
S
Ferroni
Ole P
OP
Ottersen
Mahmood
M
Amiry-Moghaddam
D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D002522:Chlorocebus aethiops; D006224:Cricetinae; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009997:Osmotic Pressure / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
C496020:AQP1 protein, human; C496030:AQP4 protein, human; C496021:Aqp1 protein, mouse; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; C486576:Trpv4 protein, mouse; D051398:Aquaporin 1; D002118:Calcium
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