Résumé
Eukaryotic protein secretion requires efficient and accurate delivery of diverse secretory and membrane proteins. This process initiates in the ER, where vesicles are sculpted by the essential COPII coat. The Sec13p subunit of the COPII coat contributes to membrane scaffolding, which enforces curvature on the nascent vesicle. A requirement for Sec13p can be bypassed when traffic of lumenally oriented membrane proteins is abrogated. Here we sought to further explore the impact of cargo proteins on vesicle formation. We show that efficient ER export of the p24 family of proteins is a major driver of the requirement for Sec13p. The scaffolding burden presented by the p24 complex is met in part by the cargo adaptor Lst1p, which binds to a subset of cargo, including the p24 proteins. We propose that the scaffolding function of Lst1p is required to generate vesicles that can accommodate difficult cargo proteins that include large oligomeric assemblies and asymmetrically distributed membrane proteins. Vesicles that contain such cargoes are also more dependent on scaffolding by Sec13p, and may serve as a model for large carrier formation in other systems.
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•Protein secretion is initiated by COPII vesicles that transport diverse cargo•Membrane scaffolding must counter underlying resistance created by “difficult” cargo•p24 family proteins represent “difficult” cargo due to their abundance and topology•The COPII cargo adaptor Lst1p contributes scaffolding to counter p24 effects
COPII vesicles bud from the ER to initiate protein secretion. D’Arcangelo et al. explore the membrane scaffolding function of the COPII coat, finding that “difficult” cargoes, which are abundant and asymmetrically distributed in the membrane, drive a requirement for scaffolding by either the Sec13p or Lst1p subunits of the coat.