Cracking Open a New Channel Family

Michael Cahalan
Courtesy of Karinne Cahalan

What lessons can hearing-channel researchers learn from a similar but ultimately successful search?

By Kerry Grens

1-3 Orai is a four-transmembrane protein with high calcium selectivity that interacts with a calcium sensor called Stim to mediate calcium influx.

CRAC bears "no channel homology, obviously, [and] no classical pore sequence," which partially explains why identifying it was such a challenge, says James Putney at the National Institute of Environmental Health. Knowing this, Fettiplace says that as far as the transduction channel goes, there's a "good possibility this is a channel that's not been characterized before."

With mutant screens for hearing defects in humans and model organisms underway, as well as attempts to develop RNA interference in hair cells, perhaps another channel family might soon emerge. Still, one key to interference screens has yet evaded hair cell researchers: readily available cultured cells. "RNA interference turned out to be the key in solving this puzzle," Cahalan says. "If you could culture hair cells, then you'd be in business."

References

1. S. Feske et al., "A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function," Nature, 441:179-85, 2006.

2. M. Vig et al., "CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry," Science, 213:1220-3, 2006.

3. A.V. Yeromin et al., "Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai," Nature, 443:226-9, 2006.

Cracking Open a New Channel Family

Nov 1, 2007

Kerry Grens

Cracking Open a New Channel Family

What lessons can hearing-channel researchers learn from a similar but ultimately successful search?

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