Study of vision disorder leads to discovery of new family of io...( Efforts to understand the most common c...)

In 1998, researchers showed that mutations in a gene that codes for the protein bestrophin were responsible for causing Best macular dystrophy, a hereditary disorder that strikes during childhood or early adolescence and causes impaired central vision. Until recently, the function of bestrophin has remained a mystery. Now, a collaborative team of Howard Hughes Medical Institute (HHMI) investigators at The Johns Hopkins University School of Medicine, has found that bestrophin is a chloride ion channel, a protein that forms a pore in cells through which charged ions can pass.

In addition to showing that bestrophin is an ion channel, the scientists searched the human genome and the DNA sequences of other organisms and found at least three other members of this chloride ion channel family in humans, four in the fruit fly and 24 in the worm Caenorhabditis elegans. None of the proteins they found had previously had a function assigned to it.

The discovery, published March 19, 2002, in the journal Proceedings of the National Academy of Sciences, is the first new chloride ion channel to be described since the cystic fibrosis transmembrane conductance regulator was discovered more than ten years ago. In addition to cystic fibrosis, mutations in chloride ion channels have been linked to several other human disorders, including diseases of the kidney and muscle.

One of the reasons it has been so long since a new chloride ion channel was discovered is that chloride channels are structurally diverse, unlike, for example, potassium channels, in which it is possible in many cases to recognize far flung family members through similarities [among the proteins], said HHMI investigator '"/>

Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
16-Apr-2002