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© The Rockefeller University Press, 0021-9525/2002/12/729-b $5.00
The Journal of Cell Biology, Volume 159, Number 5, 729-b-729

14–3-3, set me free

14–3-3 turns ER retention (left) into surface expression. Goldstein/Elsevier

The protein that does everything, 14–3-3, has now been shown to direct traffic. Ita O'Kelly, Steve Goldstein, and colleagues (Yale University, New Haven, CT) find that 14–3-3 can displace ß-COP from various proteins, thus freeing them from retention in the ER and leading to surface expression.

Goldstein set out to find proteins interacting with the COOH terminus of a K⁺ leak channel, KCNK3, and came up with a surprise: 14–3-3ß. The group also found that KCNK3 binds ß-COP, the COP1 retrieval protein, via a known dibasic motif. Binding of 14–3-3ß and ß-COP to KCNK3 was mutually exclusive. Deletion of the last residue of the 14–3-3ß binding site led to retention of all KCNK3 protein in the ER, but surface expression was rescued by a further mutation of the dibasic ß-COP binding sequence.

A similar system was demonstrated for another leak channel, an acetylcholine receptor subunit, and an MHC-associated protein. Others had individual clues in these systems about trafficking and the binding of 14–3-3 and ß-COP, but Goldstein's group is the first to put the whole story together.

For KCNK3, hormonal signals that turn on PKA may trigger the binding of 14–3-3ß to the phosphorylated channel subunit, thus increasing surface expression and decreasing the excitability of the cell. Goldstein now wants to know if such a mechanism for controlling surface expression levels is common, and what proteins act with 14–3-3 to release the grip of ER retention.

Reference:

O'Kelly, I., et al. 2002. Cell. 111:577–588.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 381K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?