Endoplasmic reticulum quality control of unassembled iron transporter depends on Rer1p-mediated retrieval from the golgi.
Endoplasmic reticulum (ER) quality control is a conserved process by which misfolded or unassembled proteins are selectively retained in the endoplasmic reticulum (ER). Failure in oligomerization of multisubunit membrane proteins is one of the events that triggers ER quality control. The transmembrane domains (TMDs) of unassembled subunits are determinants of ER retention in many cases, although the mechanism of the TMD-mediated sorting of unassembled subunits remains elusive. We studied a yeast iron transporter complex on the cell surface as a new model system for ER quality control. When Fet3p, a transmembrane subunit, is not assembled with the other membrane subunit, Ftr1p, unassembled Fet3p is exclusively localized to the ER at steady state. The TMD of Fet3p contains a determinant for this process. However, pulse-chase analysis and in vitro budding assays indicate that unassembled Fet3p rapidly escapes from the ER. Furthermore, Rer1p, a retrieval receptor for ER-resident membrane proteins in the Golgi, is responsible for the TMD-dependent ER retrieval of unassembled Fet3p. These findings provide clear evidence that the ER quality control of unassembled membrane proteins can be achieved by retrieval from the Golgi and that Rer1p serves as a specific sorting receptor in this process.
Sato
Miyuki
M
Molecular Membrane Biology Laboratory, RIKEN Discovery Research Institute, Saitama 351-0198, Japan.
Sato
Ken
K
Nakano
Akihiko
A
D002570:Ceruloplasmin / Q000378:metabolism*; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; C491137:REP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D007501:Iron; D002570:Ceruloplasmin; C085513:FET3 protein, S cerevisiae