Policing secretion: how COPII vesicles ensure stringency during protein transport
Liz Miller (MRC-LMB Cambridge)
C42 Biomedical Sciences Building
A School of Biochemistry seminar hosted by David Stephens.
Abstract: One third of the eukaryotic genome encodes secretory proteins that reach their final destination via the endoplasmic reticulum (ER). The first step in this delivery process uses transport vesicles generated by the essential COPII coat proteins. Entry into COPII vesicles represents a critical quality control checkpoint in that misfolded proteins and ER residents are generally excluded from COPII vesicles. We have characterized yeast mutants with defective ER retention, which leads us to propose a biophysical model of ER export stringency control: generation of tightly curved spherical vesicles that are filled with cargo creates steric effects that exclude non-cargo proteins. I will discuss recent unpublished findings that describe how the morphology of COPII vesicles changes in these ER quality control mutants, and how coat assembly is driven to promote vesicle formation around active sites of cargo concentration. We propose that cells must balance the efficiency of vesicle production with vesicle size and cargo occupancy to prevent inappropriate leakage of nascent proteins and ER residents.
- Hutchings J, Stancheva V, Miller EA, Zanetti G. Subtomogram averaging of COPII assemblies reveals how coat organization dictates membrane shape. Nat Commun. 2018 Oct 8;9(1):4154. doi: 10.1038/s41467-018-06577-4. PubMed PMID: 30297805; PubMed Central PMCID: PMC6175875.
- D'Arcangelo JG, Crissman J, Pagant S, Čopič A, Latham CF, Snapp EL, Miller EA. Traffic of p24 Proteins and COPII Coat Composition Mutually Influence Membrane Scaffolding. Curr Biol. 2015 May 18;25(10):1296-305. doi: 10.1016/j.cub.2015.03.029. Epub 2015 Apr 30. PubMed PMID: 25936552; PubMed Central PMCID: PMC4439346.
- Pagant S, Wu A, Edwards S, Diehl F, Miller EA. Sec24 is a coincidence detector that simultaneously binds two signals to drive ER export. Curr Biol. 2015 Feb 16;25(4):403-12. doi: 10.1016/j.cub.2014.11.070. Epub 2015 Jan 22. PubMed PMID: 25619760; PubMed Central PMCID: PMC4334704.
- Copic A, Latham CF, Horlbeck MA, D'Arcangelo JG, Miller EA. ER cargo properties specify a requirement for COPII coat rigidity mediated by Sec13p. Science. 2012 Mar 16;335(6074):1359-62. doi: 10.1126/science.1215909. Epub 2012 Feb 2. PubMed PMID: 22300850; PubMed Central PMCID: PMC3306526.
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