PMID- 16103109
OWN - NLM
STAT- MEDLINE
DCOM- 20060307
LR  - 20220223
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 19
IP  - 12
DP  - 2005 Oct
TI  - New possible roles for aquaporin-4 in astrocytes: cell cytoskeleton and 
      functional relationship with connexin43.
PG  - 1674-6
AB  - Aquaporin-4 (AQP4), the main water channel in the brain, is expressed in the 
      perivascular membranes of mouse, rat, and human astrocytes. In a previous study, 
      we used small interfering RNA (siRNA) to specifically knock down AQP4 in rat 
      astrocyte primary cultures and found that together with reduced osmotic 
      permeability, AQP4 knockdown (KD) led to altered cell morphology. However, a 
      recent report on primary cultured astrocytes from AQP4 null mice (KO) showed no 
      morphological differences compared with wild types. In this study, we compared 
      the effect of AQP4 KD in mouse, rat, and human astrocyte primary cultures and 
      found that AQP4 KD in human astrocytes resulted in a morphological phenotype 
      similar to that found in rat. In contrast, AQP4 KD in mouse astrocytes caused 
      only very mild morphological changes. The actin cytoskeleton of untreated 
      astrocytes exhibited strong species-specific differences, with F-actin being 
      organized in cortical bands in mouse and in stress fibers in rat and human 
      astrocytes. Surprisingly, as a consequence of AQP4 KD, F-actin cytoskeleton was 
      depolymerized in rat and human whereas it was completely rearranged in mouse 
      astrocytes. Although AQP4 KD induced alterations of the cell cytoskeleton, we 
      found that the expression of dystrophin (DP71), beta-dystroglycan, and 
      alpha-syntrophin was not altered. AQP4 KD in cultured mouse astrocytes produced 
      strong down-regulation of connexin43 (Cx43) with a concomitant reduction in cell 
      coupling while no major alterations in Cx43 expression were found in rat and 
      human cells. Taken together, these results demonstrate that with regard to these 
      properties, human astrocytes in culture are more similar to rat than to mouse 
      astrocytes. Moreover, even though AQP4 KD in mouse astrocytes did not result in a 
      dramatic morphological phenotype, it induced a remarkable rearrangement of 
      F-actin, not related to disruption of the dystrophin complex, indicating a 
      primary role of this water channel in the cytoskeleton changes observed. Finally, 
      the strong down-regulation of Cx43 and cell coupling in AQP4 KD mouse astrocytes 
      indicate that a functional relationship likely exists between water channels and 
      gap junctions in brain astrocytes.
FAU - Nicchia, Grazia P
AU  - Nicchia GP
AD  - Department of General and Environmental Physiology and Centre of Excellence in 
      Comparative Genomics (CEGBA), University of Bari, Bari, Italy. 
      p.nicchia@biologia.uniba.it
FAU - Srinivas, Miduturu
AU  - Srinivas M
FAU - Li, Wei
AU  - Li W
FAU - Brosnan, Celia F
AU  - Brosnan CF
FAU - Frigeri, Antonio
AU  - Frigeri A
FAU - Spray, David C
AU  - Spray DC
LA  - eng
GR  - NS41282/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050815
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Actins)
RN  - 0 (Aquaporin 4)
RN  - 0 (Connexin 43)
RN  - 0 (Dystrophin)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Aquaporin 4/*physiology
MH  - Astrocytes/*metabolism
MH  - Blotting, Western
MH  - Brain/metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Connexin 43/*biosynthesis/chemistry
MH  - Cytoskeleton/*metabolism
MH  - Down-Regulation
MH  - Dystrophin/metabolism
MH  - Electrophysiology
MH  - Gap Junctions/metabolism
MH  - Gene Silencing
MH  - Humans
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Models, Biological
MH  - Patch-Clamp Techniques
MH  - Phenotype
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Rats
MH  - Species Specificity
MH  - Time Factors
MH  - Transfection
EDAT- 2005/08/17 09:00
MHDA- 2006/03/08 09:00
CRDT- 2005/08/17 09:00
PHST- 2005/08/17 09:00 [pubmed]
PHST- 2006/03/08 09:00 [medline]
PHST- 2005/08/17 09:00 [entrez]
AID - 04-3281fje [pii]
AID - 10.1096/fj.04-3281fje [doi]
PST - ppublish
SO  - FASEB J. 2005 Oct;19(12):1674-6. doi: 10.1096/fj.04-3281fje. Epub 2005 Aug 15.