An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes.
Proc Natl Acad Sci U S A
; 108(6): 2563-8, 2011 Feb 08.
Article
in En
| MEDLINE
| ID: mdl-21262839
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 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Astrocytes
/
Cell Size
/
Aquaporin 4
/
TRPV Cation Channels
Limits:
Animals
/
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2011
Type:
Article
Affiliation country:
Italy