Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2563-8. doi: 10.1073/pnas.1012867108. Epub 2011 Jan 24.
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, M. N., Ferroni, S., Ottersen, O. P., Amiry-Moghaddam, M.,
["Institute for Nanostructured Materials, Consiglio Nazionale delle Ricerche, 40129 Bologna, Italy."]
["Institute for Nanostructured Materials, Consiglio Nazionale delle Ricerche, 40129 Bologna, Italy."]
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.
PMID: 21262839
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
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Screening
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| Experimental screening | Non-experimental screening | Reference | ||||||||
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| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPV4 |
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AQP-4 | Inference | Prediction | 21262839 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Validation: In vivo validation
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| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPV4 |
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AQP-4 | Co-immunofluorescence staining | Adult rat brain section | 21262839 | |||||
| TRPV4 |
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AQP-4 | Co-immunoprecipitation | Adult rat brain lysates | 21262839 | |||||
| TRPV4 |
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AQP-4 | Co-immunoprecipitation | DI TNC1 | Human | Full-length | Rat | Full-length | 21262839 | |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)