Membrane Protein Quantity Control at the Endoplasmic Reticulum

Ignat Printsev, Daniel Curiel, Kermit L Carraway

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The canonical function of the endoplasmic reticulum-associated degradation (ERAD) system is to enforce quality control among membrane-associated proteins by targeting misfolded secreted, intra-organellar, and intramembrane proteins for degradation. However, increasing evidence suggests that ERAD additionally functions in maintaining appropriate levels of a subset of membrane-associated proteins. In this ‘quantity control’ capacity, ERAD responds to environmental cues to regulate the proteasomal degradation of specific ERAD substrates according to cellular need. In this review, we discuss in detail seven proteins that are targeted by the ERAD quantity control system. Not surprisingly, ERAD-mediated protein degradation is a key regulatory feature of a variety of ER-resident proteins, including HMG-CoA reductase, cytochrome P450 3A4, IP3 receptor, and type II iodothyronine deiodinase. In addition, the ERAD quantity control system plays roles in maintaining the proper stoichiometry of multi-protein complexes by mediating the degradation of components that are produced in excess of the limiting subunit. Perhaps somewhat unexpectedly, recent evidence suggests that the ERAD quantity control system also contributes to the regulation of plasma membrane-localized signaling receptors, including the ErbB3 receptor tyrosine kinase and the GABA neurotransmitter receptors. For these substrates, a proportion of the newly synthesized yet properly folded receptors are diverted for degradation at the ER, and are unable to traffic to the plasma membrane. Given that receptor abundance or concentration within the plasma membrane plays key roles in determining signaling efficiency, these observations may point to a novel mechanism for modulating receptor-mediated cellular signaling.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalJournal of Membrane Biology
DOIs
StateAccepted/In press - Oct 14 2016

Keywords

  • Endoplasmic reticulum
  • ERAD pathway
  • Protein degradation
  • Quality control
  • Ubiquitination

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'Membrane Protein Quantity Control at the Endoplasmic Reticulum'. Together they form a unique fingerprint.

  • Cite this