TY - JOUR
T1 - Forward transport
T2 - 14-3-3 Binding overcomes retention in endoplasmic reticulum by dibasic signals
AU - O'Kelly, Ita
AU - Butler, Margaret H.
AU - Zilberberg, Noam
AU - Goldstein, Steve A.N.
N1 - Funding Information:
This work was supported by grants to S.A.N.G. from the NIH. We are grateful to M.J. Caplan, the anonymous reviewers, and the Editor for constructive critical feedback, R. Goldstein for assistance with graphics, and J. Crawford and T. Abbott for excellence in support of peptide synthesis and MALDI analyses.
PY - 2002/11/15
Y1 - 2002/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037112329&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(02)01040-1
DO - 10.1016/S0092-8674(02)01040-1
M3 - Article
AN - SCOPUS:0037112329
SN - 0092-8674
VL - 111
SP - 577
EP - 588
JO - Cell
JF - Cell
IS - 4
ER -