RGD Reference Report - Molecular machinery for insertion of tail-anchored membrane proteins into the endoplasmic reticulum membrane in mammalian cells. - Rat Genome Database

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Molecular machinery for insertion of tail-anchored membrane proteins into the endoplasmic reticulum membrane in mammalian cells.

Authors: Yamamoto, Yasunori  Sakisaka, Toshiaki 
Citation: Yamamoto Y and Sakisaka T, Mol Cell. 2012 Nov 9;48(3):387-97. doi: 10.1016/j.molcel.2012.08.028. Epub 2012 Oct 4.
RGD ID: 42721997
Pubmed: (View Article at PubMed) PMID:23041287
DOI: Full-text: DOI:10.1016/j.molcel.2012.08.028

Tail-anchored (TA) membrane proteins destined for the secretory pathway are posttranslationally inserted into the endoplasmic reticulum (ER) membrane, but the molecular machinery for this insertion in mammalian cells remains elusive. Here we reveal a mammalian protein complex that drives the membrane insertion. We identify calcium-modulating cyclophilin ligand (CAML) as a mammal-specific receptor for TRC40, an ATPase targeting newly synthesized TA proteins, and show that CAML mediates membrane insertion of TA proteins. We show that CAML binds to WRB, an evolutionarily conserved TRC40 receptor, through the transmembrane domains and that CAML and WRB synergistically insert TA proteins into the membrane. Mutagenesis of CAML demonstrates that binding of TRC40 to CAML is required to ensure synergistic membrane insertion. Thus, identification of CAML and WRB as components of the TRC40 receptor complex represents a crucial mechanism for driving ER membrane insertion of TA proteins in mammalian cells.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component
GET complex  (IPI)

Objects Annotated

Genes (Rattus norvegicus)
Camlg  (calcium modulating ligand)
Get1  (guided entry of tail-anchored proteins factor 1)
Get3  (guided entry of tail-anchored proteins factor 3, ATPase)


Additional Information