Hide and run. Arginine-based endoplasmic-reticulum-sorting motifs in the assembly of heteromultimeric membrane proteins
Open accessAbstract
Arginine-based endoplasmic reticulum (ER)-localization signals are sorting motifs that are involved in the biosynthetic transport of multimeric membrane proteins. After their discovery in the invariant chain of the major histocompatibility complex class II, several hallmarks of these signals have emerged. They occur in polytopic membrane proteins that are subunits of membrane protein complexes; the presence of the signal maintains improperly assembled subunits in the ER by retention or retrieval until it is masked as a result of heteromultimeric assembly. A distinct consensus sequence and their position independence with respect to the distal termini of the protein distinguish them from other ER-sorting motifs. Recognition by the coatomer (COPI) vesicle coat explains ER retrieval. Often, di-leucine endocytic signals occur close to arginine-based signals. Recruitment of 14-3-3 family or PDZ-domain proteins can counteract ER-localization activity, as can phosphorylation. This, and the occurrence of arginine-based signals in alternatively spliced regions, implicates them in the regulated surface expression of multimeric membrane proteins in addition to their function in quality control.
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RRQR motifs are thought to prevent the exit of cargo from the ER and may additionally function as ER retrieval motifs via the binding of the RRXR domain to COPI proteins.
“RRQR motifs are thought to prevent the exit of cargo from the ER and may additionally function as ER retrieval motifs via the binding of the RRXR domain to COPI proteins (Scott et al., 2001, 2003; Brock et al., 2005; Michelsen et al., 2005).”
From Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning (2011) · cites this paper as Michelsen et al., 2005
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- Authors
- Michelsen, K., Yuan, H., & Schwappach, B.
- Affiliations
- Heidelberg University (DE)
- Venue
- The EMBO Reports
- Published
- 2005-08-01
- Volume
- 6
- Issue
- 8
- Pages
- 717-722
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1369147
- OpenAlex
- W2070136749
- Cited by
- 235
- References
- 35
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 10 · 2018: 6 · 2017: 5 · 2016: 13 · 2015: 12 · 2014: 19 · 2013: 13 · 2012: 14
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- EMBO Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- GRO (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- polytopic membrane proteins, CD74, 14-3-3 proteins, PDZ domain proteins, protein phosphorylation, alternative splicing, protein quality control
- MeSH terms
- Animals, Arginine, Cell Membrane, Endocytosis, Endoplasmic Reticulum, Humans, Ions, Membrane Proteins, Models, Biological, Potassium, Protein Structure, Tertiary, Amino Acid Motifs, Protein Transport, Macromolecular Substances, 14-3-3 Proteins
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