Forward transport: 14-3-3 Binding overcomes retention in endoplasmic reticulum by dibasic signals

Ita O'Kelly, Margaret H. Butler, Noam Zilberberg, Steve A.N. Goldstein

Research output: Contribution to journalArticlepeer-review

246 Scopus citations

Abstract

Proteins with dibasic retention motifs are subject to retrograde transport to endoplasmic reticulum (ER) by COPI-coated vesicles. As forward transport requires escape from ER retention, general release mechanisms have been expected. Here, KCNK3 potassium channels are shown to bear two cytoplasmic trafficking motifs: an N-terminal dibasic site that binds β-COP to hold channels in ER and a C-terminal "release" site that binds the ubiquitous intracellular regulator 14-3-3β on a nonclassical motif in a phosphorylation-dependent fashion to suppress β-COP binding and allow forward transport. The strategy appears to be common. The major histocompatibility antigen class II-associated invariant chain Iip35 exhibits dibasic retention, carries a release motif, and shows mutually exclusive binding of β-COP and 14-3-3β on adjacent N-terminal sites. Other retained proteins are demonstrated to carry functional 14-3-3β release motifs.

Original languageEnglish
Pages (from-to)577-588
Number of pages12
JournalCell
Volume111
Issue number4
DOIs
StatePublished - 15 Nov 2002
Externally publishedYes

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