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New family of chloride ion channels discovered
  

 

Scientists have identified a new family of chloride ion channel proteins in humans, called bestrophins. One of the bestrophin proteins, hbest1, is found on the membrane of retinal cells and is associated with progressive vision loss. Also present in flies and worms, bestrophins may be important for a variety of cellular functions.


Detail from graphs showing currents from cells transfected with bestrophin cDNAs. View full

Bestrophins are the first new chloride ion channels to be reported in more than a decade. Ion channels are pores in the cell membrane through which charged ions flow. Mutations in ion channel genes can disrupt this flow and contribute to a number of human disorders, including cystic fibrosis and kidney disease.

Jeremy Nathans, a Howard Hughes Medical Institute investigator at Johns Hopkins University School of Medicine in Baltimore, led the new study. The gene for hbest1 was first described in 1998, but its function has not been known until recently.

The hBest1 protein is expressed on the part of the retina that degenerates in Best disease, also known as vitelliform macular dystrophy. The researchers determined that mutations in the hBest1 gene altered the flow of ions across cell membranes in the retina. The result is an accumulation of debris on eye tissue that can compromise vision.

Nathans' team found that the ion chloride channels are comprised of multiple bestrophin proteins. Channels consisting of normal and mutant proteins were less effective than those of normal proteins. This explains why individuals with one mutant copy and one normal copy of the hBest1 gene develop Best disease, the researchers conclude.

There are three distinct families of chloride channel proteins, and the DNA sequences of these genes do not resemble those of the bestrophins. This is one reason why their function has been a mystery for several years. Preliminary structural analyses of the proteins suggest that they are unique among chloride channels in their architecture.

Flies have at least four bestrophin proteins and worms have at least two dozen. The function of these chloride ion channels is not yet known. "The presence of these proteins throughout the animal kingdom and their large number in C. elegans suggest that bestrophin channels are likely to be involved in a wide variety of cellular processes," the researchers write in Proceedings of the National Academy of Sciences.

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Sun, H. et al. The vitelliform macular dystrophy protein defines a new family of chloride channels. Proc Natl Acad Sci USA 99, 4008-4013 (March 19, 2002).
 

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