Role of cytoplasmic C-terminal amino acids of membrane proteins in ER export.
Export of membrane proteins from the ER is believed to be selective and require transport signals, but the identity of such signals has remained elusive. The recycling type I membrane protein ERGIC-53 carries a C-terminal diphenylalanine motif that is required for efficient ER export. Here we show that this motif can be functionally substituted by a single phenylalanine or tyrosine at position -2, two leucines or isoleucines at position -1 and -2 or a single valine at position -1. These motifs are common among mammalian type I membrane proteins. A single C-terminal valine, but none of the other motifs, accelerates transport of inefficiently exported reporter constructs and hence operates as an export signal. The valine signal is position, but not context, dependent. All transport motifs mediate COPII binding in vitro with distinct preferences for the COPII subunits Sec23p, Sec24Bp, Sec24Cp and p125. These results suggest that cytoplasmic C-terminal amino-acid motifs, either alone or in conjunction with other transport determinants, accelerate ER export of numerous type I and probably polytopic membrane proteins by mediating interaction with COPII coat components.
Nufer
Oliver
O
Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Guldbrandsen
Svend
S
Degen
Martin
M
Kappeler
Felix
F
Paccaud
Jean-Pierre
JP
Tani
Katsuko
K
Hauri
Hans-Peter
HP
D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D037241:Mannose-Binding Lectins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D011485:Protein Binding; D021382:Protein Sorting Signals; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology*; D014633:Valine / Q000378:metabolism
C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D021122:Protein Subunits; D010649:Phenylalanine; D014633:Valine