Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

ER retention is imposed by COPII protein sorting and attenuated by 4-phenylbutyrate

Journal Article · · eLife
DOI:https://doi.org/10.7554/elife.26624· OSTI ID:1628870
 [1];  [2];  [3]
  1. Memorial Sloan Kettering Cancer Center, New York, NY (United States); DOE/OSTI
  2. Memorial Sloan Kettering Cancer Center, New York, NY (United States)
  3. Memorial Sloan Kettering Cancer Center, New York, NY (United States); Howard Hughes Medical Inst., New York, NY (United States)
+ Show Author Affiliations

Native cargo proteins exit the endoplasmic reticulum (ER) in COPII-coated vesicles, whereas resident and misfolded proteins are substantially excluded from vesicles by a retention mechanism that remains unresolved. We probed the ER retention process using the proteostasis regulator 4-phenylbutyrate (4-PBA), which we show targets COPII protein to reduce the stringency of retention. 4-PBA competes with p24 proteins to bind COPII. When p24 protein uptake is blocked, COPII vesicles package resident proteins and an ER-trapped mutant LDL receptor. We further show that 4-PBA triggers the secretion of a KDEL-tagged luminal resident, implying that a compromised retention mechanism causes saturation of the KDEL retrieval system. The results indicate that stringent ER retention requires the COPII coat machinery to actively sort biosynthetic cargo from diffusible misfolded and resident ER proteins.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH); Howard Hughes Medical Institute; Memorial Sloan-Kettering Cancer Center
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1628870
Journal Information:
eLife, Journal Name: eLife Vol. 6; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English

References (66)

Semi-intact cells permeable to macromolecules: Use in reconstitution of protein transport from the endoplasmic reticulum to the Golgi complex journal August 1987
COPII: A membrane coat formed by Sec proteins that drive vesicle budding from the endoplasmic reticulum journal June 1994
Vesicular stomatitis virus glycoprotein is sorted and concentrated during export from the endoplasmic reticulum journal March 1994
Vesicular Tubular Clusters between the ER and Golgi Mediate Concentration of Soluble Secretory Proteins by Exclusion from COPI-Coated Vesicles journal July 1999
Coupling of Coat Assembly and Vesicle Budding to Packaging of Putative Cargo Receptors journal February 1999
Giving protein traffic the green light journal June 2000
Structural basis of cargo membrane protein discrimination by the human COPII coat machinery journal October 2008
Intrauterine exposure to low-dose DBP in the mice induces obesity in offspring via suppression of UCP1 mediated ER stress journal October 2020
An integral membrane component of coatomer-coated transport vesicles defines a family of proteins involved in budding. journal August 1995
Thinking about p24 proteins and how transport vesicles select their cargo journal April 2000
A Di-acidic (D X E) Code Directs Concentration of Cargo during Export from the Endoplasmic Reticulum journal May 1999
Uncoupled Packaging of Amyloid Precursor Protein and Presenilin 1 into Coat Protein Complex II Vesicles journal December 2004
Retention of Mutant Low Density Lipoprotein Receptor in Endoplasmic Reticulum (ER) Leads to ER Stress journal October 2005
Recycling of proteins from the Golgi compartment to the ER in yeast. journal August 1990
Interactions between Newly Synthesized Glycoproteins, Calnexin and a Network of Resident Chaperones in the Endoplasmic Reticulum journal February 1997
p24 Proteins and Quality Control of LIN-12 and GLP-1 Trafficking in Caenorhabditis elegans journal June 1999
Distinct retrieval and retention mechanisms are required for the quality control of endoplasmic reticulum protein folding journal October 2001
Concentrative sorting of secretory cargo proteins into COPII-coated vesicles journal December 2002
Correction: Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response journal February 2021
The Erv41–Erv46 complex serves as a retrograde receptor to retrieve escaped ER proteins journal January 2015
Protein sorting at the ER–Golgi interface journal November 2016
Deletion of Yeast p24 Genes Activates the Unfolded Protein Response journal April 2001
Membrane protein retrieval from the Golgi apparatus to the endoplasmic reticulum (ER): characterization of the RER1 gene product as a component involved in ER localization of Sec12p. journal November 1995
Identification of Potential Regulatory Elements for the Transport of Emp24p journal December 1998
A Subset of Chaperones and Folding Enzymes Form Multiprotein Complexes in Endoplasmic Reticulum to Bind Nascent Proteins journal December 2002
Suppression of Coatomer Mutants by a New Protein Family with COPI and COPII Binding Motifs in Saccharomyces cerevisiae journal August 2003
Misfolded Proteins Traffic from the Endoplasmic Reticulum (ER) Due to ER Export Signals journal February 2007
Sec24C/D-isoform–specific sorting of the preassembled ER–Golgi Q-SNARE complex journal September 2016
The KDEL receptor mediates a retrieval mechanism that contributes to quality control at the endoplasmic reticulum journal June 2001
Defective Trafficking of Nephrin Missense Mutants Rescued by a Chemical Chaperone journal July 2004
4-Phenylbutyrate restores the functionality of a misfolded mutant low-density lipoprotein receptor: Rescue of mutant low-density lipoprotein receptor journal March 2007
Adapting Proteostasis for Disease Intervention journal February 2008
ER Cargo Properties Specify a Requirement for COPII Coat Rigidity Mediated by Sec13p journal February 2012
Cargo Capture and Bulk Flow in the Early Secretory Pathway journal October 2016
In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR. journal November 1997
Phenylacetylglutamine May Replace Urea as a Vehicle for Waste Nitrogen Excretion journal February 1991
Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control journal May 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution. text January 2010
A C-terminal signal prevents secretion of luminal ER proteins journal March 1987
Vesicular stomatitis virus glycoprotein is sorted and concentrated during export from the endoplasmic reticulum journal March 1994
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Vesicular Tubular Clusters between the ER and Golgi Mediate Concentration of Soluble Secretory Proteins by Exclusion from COPI-Coated Vesicles journal July 1999
Coupling of Coat Assembly and Vesicle Budding to Packaging of Putative Cargo Receptors journal February 1999
SNARE Selectivity of the COPII Coat journal August 2003
Multiple Cargo Binding Sites on the COPII Subunit Sec24p Ensure Capture of Diverse Membrane Proteins into Transport Vesicles journal August 2003
Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization journal September 2004
The Transport Signal on Sec22 for Packaging into COPII-Coated Vesicles Is a Conformational Epitope journal May 2007
Dynamics and retention of misfolded proteins in native ER membranes journal April 2000
Uncoupled Packaging of Amyloid Precursor Protein and Presenilin 1 into Coat Protein Complex II Vesicles journal December 2004
Retention of Mutant Low Density Lipoprotein Receptor in Endoplasmic Reticulum (ER) Leads to ER Stress journal October 2005
Erv41p and Erv46p journal January 2001
Quality control in the secretory pathway: retention of a misfolded viral membrane glycoprotein involves cycling between the ER, intermediate compartment, and Golgi apparatus. journal July 1994
Biogenesis of γ-secretase early in the secretory pathway journal December 2007
Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response journal November 2009
Genes that control the fidelity of endoplasmic reticulum to Golgi transport identified as suppressors of vesicle budding mutations. journal July 1996
A Subset of Chaperones and Folding Enzymes Form Multiprotein Complexes in Endoplasmic Reticulum to Bind Nascent Proteins journal December 2002
Suppression of Coatomer Mutants by a New Protein Family with COPI and COPII Binding Motifs in Saccharomyces cerevisiae journal August 2003
Misfolded Proteins Traffic from the Endoplasmic Reticulum (ER) Due to ER Export Signals journal February 2007
Sec24C/D-isoform–specific sorting of the preassembled ER–Golgi Q-SNARE complex journal September 2016
Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate journal June 2016
Defective Trafficking of Nephrin Missense Mutants Rescued by a Chemical Chaperone journal July 2004
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes journal August 2006
Topical Ocular Sodium 4-Phenylbutyrate Rescues Glaucoma in a Myocilin Mouse Model of Primary Open-Angle Glaucoma journal March 2012
In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR. journal November 1997
Role of cytoplasmic C-terminal amino acids of membrane proteins in ER export journal February 2002

Cited By (5)

How to Avoid a No-Deal ER Exit journal September 2019
Proteomic Profiling of Mammalian COPII Vesicles posted_content January 2018
Proximity-dependent proteomics of the Chlamydia trachomatis inclusion membrane reveals functional interactions with endoplasmic reticulum exit sites posted_content March 2018
COPII gets in shape: Lessons derived from morphological aspects of early secretion journal August 2018
Proximity-dependent proteomics of the Chlamydia trachomatis inclusion membrane reveals functional interactions with endoplasmic reticulum exit sites journal April 2019

Similar Records

COPII-coated membranes function as transport carriers of intracellular procollagen I
Journal Article · Thu Apr 20 00:00:00 EDT 2017 · Journal of Cell Biology · OSTI ID:1352291
The Transport Signal on Sec22 for Packaging into COPII-Coated Vesicles is a Conformational Epitope
Journal Article · Sun Dec 31 23:00:00 EST 2006 · Molecular Cell · OSTI ID:930475
TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats
Journal Article · Mon Aug 22 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1322365

Related Subjects

60 APPLIED LIFE SCIENCES
Life Sciences & Biomedicine - Other Topics