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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:
Howard Hughes Medical Institute; Memorial Sloan-Kettering Cancer Center; National Institutes of Health (NIH); USDOE Office of Science (SC)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1628870
Alternate ID(s):
OSTI ID: 1847657
OSTI ID: 1856418
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

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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

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