Tail-anchored and signal-anchored proteins utilize overlapping pathways during membrane insertion.
Tail-anchored proteins are a distinct class of membrane proteins that are characterized by a C-terminal membrane insertion sequence and a capacity for post-translational integration. Although it is now clear that tail-anchored proteins are inserted into the membrane at the endoplasmic reticulum (ER), the molecular basis for their integration is poorly understood. We have used a cross-linking approach to identify ER components that may be involved in the membrane insertion of tail-anchored proteins. We find that several newly synthesized tail-anchored proteins are transiently associated with a defined subset of cellular components. Among these, we identify several ER proteins, including subunits of the Sec61 translocon, Sec62p, Sec63p, and the 25-kDa subunit of the signal peptidase complex. When we analyze the cotranslational membrane insertion of a comparable signal-anchored protein we find the nascent polypeptide associated with a similar set of ER components. We conclude that the pathways for the integration of tail-anchored and signal-anchored membrane proteins at the ER exhibit a substantial degree of overlap, and we propose that this reflects similarities between co- and post-translational membrane insertion.
Abell
Benjamin M
BM
School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Jung
Martin
M
Oliver
Jason D
JD
Knight
Bruce C
BC
Tyedmers
Jens
J
Zimmermann
Richard
R
High
Stephen
S
D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure*; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D000069816:SEC Translocation Channels; D015398:Signal Transduction; D014158:Transcription, Genetic
D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D011994:Recombinant Proteins; D000069816:SEC Translocation Channels