14–3-3, set me free

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 β-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: 14–3-3β. The group also found that KCNK3 binds β-COP, the COP1 retrieval protein, via a known dibasic motif. Binding of 14–3-3β and β-COP to KCNK3 was mutually exclusive. Deletion of the last residue of the 14–3-3β binding site led to retention of all KCNK3 protein in the ER, but surface expression was rescued by a further mutation of the dibasic β-COP binding sequence.

A similar system...