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.
Benfenati V., Caprini M., Dovizio M., Mylonakou M.N., Ferroni S., Ottersen O.P., et al. (2011). An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108(6), 2563-2568 [10.1073/pnas.1012867108].
An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes.
BENFENATI, VALENTINA;CAPRINI, MARCO;FERRONI, STEFANO;
2011
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
