Faculty Opinions recommendation of Sorting of GPI-anchored proteins into ER exit sites by p24 proteins is dependent on remodeled GPI.

Glycosylphosphatidylinositol (GPI) anchoring of proteins is a posttranslational modification occurring in the endoplasmic reticulum (ER). After GPI attachment, proteins are transported by coat protein complex II (COPII)-coated vesicles from the ER. Because GPI-anchored proteins (GPI-APs) are localized in the lumen, they cannot interact with cytosolic COPII components directly. Receptors that link GPI-APs to COPII are thought to be involved in efficient packaging of GPI-APs into vesicles; however, mechanisms of GPI-AP sorting are not well understood. Here we describe two remodeling reactions for GPI anchors, mediated by PGAP1 and PGAP5, which were required for sorting of GPI-APs to ER exit sites. The p24 family of proteins recognized the remodeled GPI-APs and sorted them into COPII vesicles. Association of p24 proteins with GPI-APs was pH dependent, which suggests that they bind in the ER and dissociate in post-ER acidic compartments. Our results indicate that p24 complexes act as cargo receptors for correctly remodeled GPI-APs to be sorted into COPII vesicles.

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Faculty Opinions recommendation of High-curvature domains of the ER are important for the organization of ER exit sites in Saccharomyces cerevisiae.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717957526.793500658 ◽

2014 ◽

Author(s):

Blanche Schwappach ◽

Eric Clement Arakel

Keyword(s):

Saccharomyces Cerevisiae ◽

Er Exit Sites

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Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export

The Journal of Cell Biology ◽

10.1083/jcb.201312062 ◽

2014 ◽

Vol 206 (6) ◽

pp. 751-762 ◽

Cited By ~ 66

Author(s):

Kota Saito ◽

Koh Yamashiro ◽

Noriko Shimazu ◽

Tomoya Tanabe ◽

Kenji Kontani ◽

...

Keyword(s):

Direct Interaction ◽

Secretory Proteins ◽

Nucleotide Exchange ◽

Guanine Nucleotide Exchange ◽

Transport Vesicles ◽

Nucleotide Exchange Factor ◽

Receptor Component ◽

Er Exit Sites ◽

Guanosine Triphosphatase ◽

Trimeric Structure

Mechanisms for exporting variably sized cargo from the endoplasmic reticulum (ER) using the same machinery remain poorly understood. COPII-coated vesicles, which transport secretory proteins from the ER to the Golgi apparatus, are typically 60–90 nm in diameter. However, collagen, which forms a trimeric structure that is too large to be accommodated by conventional transport vesicles, is also known to be secreted via a COPII-dependent process. In this paper, we show that Sec12, a guanine-nucleotide exchange factor for Sar1 guanosine triphosphatase, is concentrated at ER exit sites and that this concentration of Sec12 is specifically required for the secretion of collagen VII but not other proteins. Furthermore, Sec12 recruitment to ER exit sites is organized by its direct interaction with cTAGE5, a previously characterized collagen cargo receptor component, which functions together with TANGO1 at ER exit sites. These findings suggest that the export of large cargo requires high levels of guanosine triphosphate–bound Sar1 generated by Sec12 localized at ER exit sites.

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A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation

eLife ◽

10.7554/elife.04132 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 29

Author(s):

Margarita Zacharogianni ◽

Angelica Aguilera-Gomez ◽

Tineke Veenendaal ◽

Jan Smout ◽

Catherine Rabouille

Keyword(s):

Amino Acid ◽

Cell Viability ◽

Secretory Pathway ◽

Protein Transport ◽

Liquid Droplet ◽

Protein Translation ◽

Amino Acid Starvation ◽

Early Secretory Pathway ◽

Er Exit Sites ◽

Nutritional Restriction

Nutritional restriction leads to protein translation attenuation that results in the storage and degradation of free mRNAs in cytoplasmic assemblies. In this study, we show in Drosophila S2 cells that amino-acid starvation also leads to the inhibition of another major anabolic pathway, the protein transport through the secretory pathway, and to the formation of a novel reversible non-membrane bound stress assembly, the Sec body that incorporates components of the ER exit sites. Sec body formation does not depend on membrane traffic in the early secretory pathway, yet requires both Sec23 and Sec24AB. Sec bodies have liquid droplet-like properties, and they act as a protective reservoir for ERES components to rebuild a functional secretory pathway after re-addition of amino-acids acting as a part of a survival mechanism. Taken together, we propose that the formation of these structures is a novel stress response mechanism to provide cell viability during and after nutrient stress.

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ER exit sites in Drosophila display abundant ER-Golgi vesicles and pearled tubes but no megacarriers

Cell Reports ◽

10.1016/j.celrep.2021.109707 ◽

2021 ◽

Vol 36 (11) ◽

pp. 109707

Author(s):

Ke Yang ◽

Min Liu ◽

Zhi Feng ◽

Marta Rojas ◽

Lingjian Zhou ◽

...

Keyword(s):

Golgi Vesicles ◽

Er Exit Sites

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Vesicular and uncoated Rab1-dependent cargo carriers facilitate ER to Golgi transport

Journal of Cell Science ◽

10.1242/jcs.239814 ◽

2020 ◽

Vol 133 (14) ◽

pp. jcs239814 ◽

Cited By ~ 1

Author(s):

Laura M. Westrate ◽

Melissa J. Hoyer ◽

Michael J. Nash ◽

Gia K. Voeltz

Keyword(s):

Endoplasmic Reticulum ◽

De Novo ◽

Coated Vesicle ◽

First Person ◽

Coat Proteins ◽

Animal Cells ◽

Golgi Transport ◽

Er Exit Sites ◽

Copii Vesicles ◽

Export System

ABSTRACTSecretory cargo is recognized, concentrated and trafficked from endoplasmic reticulum (ER) exit sites (ERES) to the Golgi. Cargo export from the ER begins when a series of highly conserved COPII coat proteins accumulate at the ER and regulate the formation of cargo-loaded COPII vesicles. In animal cells, capturing live de novo cargo trafficking past this point is challenging; it has been difficult to discriminate whether cargo is trafficked to the Golgi in a COPII-coated vesicle. Here, we describe a recently developed live-cell cargo export system that can be synchronously released from ERES to illustrate de novo trafficking in animal cells. We found that components of the COPII coat remain associated with the ERES while cargo is extruded into COPII-uncoated, non-ER associated, Rab1 (herein referring to Rab1a or Rab1b)-dependent carriers. Our data suggest that, in animal cells, COPII coat components remain stably associated with the ER at exit sites to generate a specialized compartment, but once cargo is sorted and organized, Rab1 labels these export carriers and facilitates efficient forward trafficking.This article has an associated First Person interview with the first author of the paper.

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p24 proteins, intracellular trafficking, and behavior: Drosophila melanogaster provides insights and opportunities

Biology of the Cell ◽

10.1111/j.1768-322x.2004.tb01415.x ◽

2004 ◽

Vol 96 (4) ◽

pp. 271-278 ◽

Cited By ~ 34

Author(s):

Ginger E. Carney ◽

Nathan J. Bowen

Keyword(s):

Drosophila Melanogaster ◽

Intracellular Trafficking ◽

And Behavior ◽

P24 Proteins

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Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects

Human Vaccines & Immunotherapeutics ◽

10.1080/21645515.2015.1026500 ◽

2015 ◽

Vol 11 (6) ◽

pp. 1540-1556 ◽

Cited By ~ 3

Author(s):

Shannon R Roff ◽

Missa P Sanou ◽

Mobeen H Rathore ◽

Jay A Levy ◽

Janet K Yamamoto

Keyword(s):

Hiv 1 ◽

P24 Proteins

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How to Avoid a No-Deal ER Exit

Cells ◽

10.3390/cells8091051 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1051 ◽

Cited By ~ 2

Author(s):

Tiziana Anelli ◽

Paola Panina-Bordignon

Keyword(s):

Quality Control ◽

Protein Folding ◽

Protein Concentration ◽

Secretory Proteins ◽

Protein Accumulation ◽

Secreted Protein ◽

Native Structure ◽

Golgi Compartment ◽

Abnormal Increase ◽

Er Exit Sites

Efficiency and fidelity of protein secretion are achieved thanks to the presence of different steps, located sequentially in time and space along the secretory compartment, controlling protein folding and maturation. After entering into the endoplasmic reticulum (ER), secretory proteins attain their native structure thanks to specific chaperones and enzymes. Only correctly folded molecules are allowed by quality control (QC) mechanisms to leave the ER and proceed to downstream compartments. Proteins that cannot fold properly are instead retained in the ER to be finally destined to proteasomal degradation. Exiting from the ER requires, in most cases, the use of coated vesicles, departing at the ER exit sites, which will fuse with the Golgi compartment, thus releasing their cargoes. Protein accumulation in the ER can be caused by a too stringent QC or by ineffective transport: these situations could be deleterious for the organism, due to the loss of the secreted protein, and to the cell itself, because of abnormal increase of protein concentration in the ER. In both cases, diseases can arise. In this review, we will describe the pathophysiology of protein folding and transport between the ER and the Golgi compartment.

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