ArticleMolecular biology of the cell2000
Down-regulation of cell surface receptors is modulated by polar residues within the transmembrane domain.
Article in Molecular biology of the cell, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Role of vaspin in porcine ovary: effect on signaling pathways and steroid synthesis via GRP78 receptor and protein kinase A†.Biology of reproduction · 2020Article
- The CD28 Transmembrane Domain Contains an Essential Dimerization Motif.Frontiers in immunology · 2020Article
- Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation.American journal of human genetics · 2018Article
- Protein homeostasis at the plasma membrane.Physiology (Bethesda, Md.) · 2014Review
- Anchors aweigh: protein localization and transport mediated by transmembrane domains.Trends in cell biology · 2013Review
- Residues in the hendra virus fusion protein transmembrane domain are critical for endocytic recycling.Journal of virology · 2012Article
- Rabenosyn-5 defines the fate of the transferrin receptor following clathrin-mediated endocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Derlin-dependent retrograde transport from endosomes to the Golgi apparatus.Traffic (Copenhagen, Denmark) · 2011Article
- Protein quality control at the plasma membrane.Current opinion in cell biology · 2011Review
- Quality control for unfolded proteins at the plasma membrane.The Journal of cell biology · 2010Article
- Reovirus FAST protein transmembrane domains function in a modular, primary sequence-independent manner to mediate cell-cell membrane fusion.Journal of virology · 2009Article
- Targeting of pseudorabies virus structural proteins to axons requires association of the viral Us9 protein with lipid rafts.PLoS pathogens · 2008Article
- Enhanced cell-surface stability of rescued DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) by pharmacological chaperones.The Biochemical journal · 2008Article
- Article
- Role of the endocytic machinery in the sorting of lysosome-associated membrane proteins.Molecular biology of the cell · 2005Article
- Parvovirus infection of cells by using variants of the feline transferrin receptor altering clathrin-mediated endocytosis, membrane domain localization, and capsid-binding domains.Journal of virology · 2004Article
- Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins.The EMBO journal · 2004Article
- Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes.The Journal of cell biology · 2004Article
- Rer1p, a retrieval receptor for ER membrane proteins, recognizes transmembrane domains in multiple modes.Molecular biology of the cell · 2003Article
- Recognition of a single transmembrane degron by sequential quality control checkpoints.Molecular biology of the cell · 2003Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
How recycling receptors are segregated from down-regulated receptors in the endosome is unknown. In previous studies, we demonstrated that substitutions in the transferrin receptor (TR) transmembrane domain (TM) convert the protein from an efficiently recycling receptor to one that is rapidly down regulated. In this study, we demonstrate that the "signal" within the TM necessary and sufficient for down-regulation is Thr(11)Gln(17)Thr(19) (numbering in TM). Transplantation of these polar residues into the wild-type TR promotes receptor down-regulation that can be demonstrated by changes in protein half-life and in receptor recycling. Surprisingly, this modification dramatically increases the TR internalization rate as well ( approximately 79% increase). Sucrose gradient centrifugation and cross-linking studies reveal that propensity of the receptors to self-associate correlates with down-regulation. Interestingly, a number of cell surface proteins that contain TM polar residues are known to be efficiently down-regulated, whereas recycling receptors for low-density lipoprotein and transferrin conspicuously lack these residues. Our data, therefore, suggest a simple model in which specific residues within the TM sequences dramatically influence the fate of membrane proteins after endocytosis, providing an alternative signal for down-regulation of receptor complexes to the well-characterized cytoplasmic tail targeting signals.
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