Cargo crowding contributes to sorting stringency in COPII vesicles

Natalia Gomez-Navarro, Alejandro Melero, Xiao Han Li, Jérôme Boulanger, Wanda Kukulski, Elizabeth A. Miller (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Accurate maintenance of organelle identity in the secretory pathway relies on retention and retrieval of resident proteins. In the endoplasmic reticulum (ER), secretory proteins are packaged into COPII vesicles that largely exclude ER residents and misfolded proteins by mechanisms that remain unresolved. Here we combined biochemistry and genetics with correlative light and electron microscopy (CLEM) to explore how selectivity is achieved. Our data suggest that vesicle occupancy contributes to ER retention: in the absence of abundant cargo, nonspecific bulk flow increases. We demonstrate that ER leakage is influenced by vesicle size and cargo occupancy: overexpressing an inert cargo protein or reducing vesicle size restores sorting stringency. We propose that cargo recruitment into vesicles creates a crowded lumen that drives selectivity. Retention of ER residents thus derives in part from the biophysical process of cargo enrichment into a constrained spherical membrane-bound carrier.

Original languageEnglish
Article numbere201806038
Number of pages20
JournalJournal of Cell Biology
Volume219
Issue number7
Early online date13 May 2020
DOIs
Publication statusPublished - 6 Jul 2020

ASJC Scopus subject areas

  • Cell Biology

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