ER-to-Golgi trafficking of procollagen in the absence of large carriers

McCaughey, Janine; Stevenson, Nicola; Cross, Stephen; Stephens, David

doi:10.1083/jcb.201806035

Cited by 86 publications

(95 citation statements)

References 78 publications

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“…The collagen export receptor, TANGO1, has been proposed to drive coat organization to favor tubule formation around an exportcompetent collagen fiber (Saito et al, 2009;Raote et al, 2018). However, other modes of collagen export have also been proposed, where local membrane fusion and remodeling might occur (Malhotra and Erlmann, 2015;McCaughey et al, 2019). Whether and how ER resident proteins are excluded from such structures remain to be fully explored.…”

Section: Vesicle Size and Cargo Occupancy As Drivers Of Quality Controlmentioning

confidence: 99%

Cargo crowding contributes to sorting stringency in COPII vesicles

Gómez-Navarro

Melero

et al. 2020

Journal of Cell Biology

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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.

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Section: Vesicle Size and Cargo Occupancy As Drivers Of Quality Controlmentioning

confidence: 99%

Cargo crowding contributes to sorting stringency in COPII vesicles

Gómez-Navarro

Melero

et al. 2020

Journal of Cell Biology

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“…The collagen export receptor, TANGO1, has been proposed to drive coat organization to favour tubule formation around an export-competent collagen fibre. However, other modes of collagen export have also been proposed, where local membrane fusion and remodelling might occur (Malhotra and Erlmann, 2015;McCaughey et al, 2019). Whether and how ER resident proteins are excluded from such structures remains to be fully explored.…”

Section: Coat Composition Drives Vesicle Morphologymentioning

confidence: 99%

Cargo crowding drives sorting stringency in COPII vesicles

Gómez-Navarro

Melero

Boulanger

et al. 2020

Preprint

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Combining correlative light and electron microscopy with yeast genetics and biochemistry, Gomez-Navarro, Melero and colleagues show that cargo recruitment into a constrained COPII vesicle restricts bulk flow, thereby contributing to sorting stringency and ER quality control. AbstractAccurate 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 dictates ER retention: in the absence of abundant cargo, non-specific 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 lumenal steric pressure that drives selectivity. Sorting stringency is thus an emergent property of the biophysical process of cargo enrichment into a constrained spherical membrane-bound carrier.

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“…Bulky cargoes such as collagen are also observed in ER-derived tubular carrier [40,41], although little is known about the molecular nature of the synthesis, transport, and fusion with target membranes of these tubular carriers. Finally, the secretion of collagen may not even require intermediate carriers as direct connections between ER and ERGIC membranes may allow the direct export of collagen [42].…”

Section: Vesicle Buddingmentioning

confidence: 99%

ER-to-Golgi Trafficking and Its Implication in Neurological Diseases

Wang

Stanford

Kundu

2020

Cells

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Membrane and secretory proteins are essential for almost every aspect of cellular function. These proteins are incorporated into ER-derived carriers and transported to the Golgi before being sorted for delivery to their final destination. Although ER-to-Golgi trafficking is highly conserved among eukaryotes, several layers of complexity have been added to meet the increased demands of complex cell types in metazoans. The specialized morphology of neurons and the necessity for precise spatiotemporal control over membrane and secretory protein localization and function make them particularly vulnerable to defects in trafficking. This review summarizes the general mechanisms involved in ER-to-Golgi trafficking and highlights mutations in genes affecting this process, which are associated with neurological diseases in humans. OverviewApproximately one-third of all proteins encoded by the mammalian genome are exported from the endoplasmic reticulum (ER) and transported to the Golgi apparatus, where they are sorted for delivery to their final destination in membrane compartments or secretory vesicles [1]. Secretory proteins are co-translationally inserted into the ER and then packaged into transport vesicles at ER exit sites (ERES, also known as the transitional ER), which are specialized regions of smooth ER [1].The stepwise process for segregating and exporting cargo from the ER is similar in yeast, plant, and mammalian cells and relies on several essential proteins (SAR1-GTPase, SEC23, SEC24, SEC13, and SEC31). The first step involves the conversion of SAR1-GDP to SAR1-GTP by the guanine nucleotide exchange factor SEC12, which resides in the ER membrane [2,3]. This results in the localization of SAR1-GTP to the ER membrane, triggering the recruitment of SEC23/24 heterodimers [4]. The membrane localization of the SEC23/24 heterodimers promotes the entrapment of cargo by SEC24 and the recruitment of SEC13/31 heterotetramers. The sequential binding of SEC13/31 heterotetramers to SAR1-GTP-SEC23/24 complexes drives the formation of a cage-like lattice [4][5][6][7]. Although the basic steps involved in generating COPII vesicles are well understood and can be reconstituted in vitro, additional proteins are involved in regulating the process in cells. Differences between yeast and mammalian ER-to-Golgi trafficking include the presence of multiple COPII protein isoforms and an ER-Golgi intermediate compartment (ERGIC) in mammals, which likely evolved to help meet the cell-type-specific demands of multicellular organisms.Unlike other cell types, neurons consist of two compartments: the somatodendritic compartment and the axonal compartment. These compartments are separated by the axonal-exclusion zone located at the base of the axon, where proteins are either permitted into or excluded from the axon. Neurons are

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ER-to-Golgi trafficking of procollagen in the absence of large carriers

Cited by 86 publications

References 78 publications

Cargo crowding contributes to sorting stringency in COPII vesicles

Cargo crowding contributes to sorting stringency in COPII vesicles

Cargo crowding drives sorting stringency in COPII vesicles

ER-to-Golgi Trafficking and Its Implication in Neurological Diseases

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