Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals.
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 beta-COP to hold channels in ER and a C-terminal "release" site that binds the ubiquitous intracellular regulator 14-3-3beta on a nonclassical motif in a phosphorylation-dependent fashion to suppress beta-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 beta-COP and 14-3-3beta on adjacent N-terminal sites. Other retained proteins are demonstrated to carry functional 14-3-3beta release motifs.
O'Kelly
Ita
I
Yale University School of Medicine, Department of Pediatrics, Department of Cellular and Molecular Physiology, Boyer Center for Molecular Medicine, New Haven, CT 06536, USA.
Butler
Margaret H
MH
Zilberberg
Noam
N
Goldstein
Steve A N
SA
D048948:14-3-3 Proteins; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D020756:Coatomer Protein / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins; D010455:Peptides / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D021381:Protein Transport; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D014633:Valine / Q000378:metabolism
D048948:14-3-3 Proteins; D020756:Coatomer Protein; D009419:Nerve Tissue Proteins; D010455:Peptides; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C482982:YWHAB protein, human; C420132:potassium channel subfamily K member 3; D014446:Tyrosine 3-Monooxygenase; D014633:Valine