Clue to genetic cause for high blood pressure
February 2007
Scientists looking into rocketing blood pressure have caught a cell’s reaction to salt on film. The images show proteins marshalling themselves within a cell which is being threatened by dangerously high salt levels. The footage was captured as researchers were examining a rare genetic condition called Gordon’s Syndrome that causes exceptionally high blood pressure.
Mutations in two genes send blood pressure spiralling upwards in people who have the syndrome. By observing normal versions of the proteins, scientists were able to identify a cellular protein called WNK1 that appears to help regulate blood pressure in us all.
Now, scientists led by Dr Dario Alessi at the MRC Protein Phosphorylation Unit in Dundee have captured WNK1 in action on film.
Blood pressure regulation is already known to be linked to salt levels. If too much salt is present, blood pressure can become dangerously high. The experiment shown in the video mimics the effect of a high salt concentration on body cells. It hints at how the body controls blood pressure at a cellular level.
Still from microscope video footage.
Download the microscope film footage (wnk1.mpg, 20secs, 1.7mg) to watch as the WNK1 proteins dramatically reorganise themselves inside the cell as salt levels soar outside.
At the beginning of the film when salt levels are normal the WNK1 protein (shown in green) is evenly distributed in spaces between the internal structures of the cell. Within seconds of more salt (labelled NaCl in the video) being added, the protein rapidly alters its position by moving to surround internal cell structures. The protein stays next to cell structures as long as salt levels remain high. The scientists’ next job is to figure out exactly why the proteins do this.
Dr Alessi explains:
‘‘We believe that when cells are exposed to too high a salt environment, the movement of WNK1 to internal cell structures could be the switch for a series of molecular pathways that play important roles in enabling a cell to tolerate and respond appropriately to such conditions. Humans that have mutations in the WNK1 gene may have altered ability to mount such responses and this in turn might result in increased blood pressure.’’
He concludes:
‘‘We are now trying to understand the exact importance of the rapid movement of WNK1 within cells. Our data and the protein’s striking response suggest that the WNK1 enzyme is an important sensor of salt levels outside cells.’’
Original research paper: Regulation of activity and localisation of the WNK1 protein kinase by hyperosmotic stress was published in Journal of Cell Biology on 1 January 2007.
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