Faculty Opinions recommendation of Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile.

ABSTRACT Saccharomyces cerevisiae Grx6 and Grx7 are two monothiol glutaredoxins whose active-site sequences (CSYS and CPYS, respectively) are reminiscent of the CPYC active-site sequence of classical dithiol glutaredoxins. Both proteins contain an N-terminal transmembrane domain which is responsible for their association to membranes of the early secretory pathway vesicles, facing the luminal side. Thus, Grx6 localizes at the endoplasmic reticulum and Golgi compartments, while Grx7 is mostly at the Golgi. Expression of GRX6 is modestly upregulated by several stresses (calcium, sodium, and peroxides) in a manner dependent on the Crz1-calcineurin pathway. Some of these stresses also upregulate GRX7 expression under the control of the Msn2/4 transcription factor. The N glycosylation inhibitor tunicamycin induces the expression of both genes along with protein accumulation. Mutants lacking both glutaredoxins display reduced sensitivity to tunicamycin, although the drug is still able to manifest its inhibitory effect on a reporter glycoprotein. Grx6 and Grx7 have measurable oxidoreductase activity in vivo, which is increased in the presence of tunicamycin. Both glutaredoxins could be responsible for the regulation of the sulfhydryl oxidative state at the oxidant conditions of the early secretory pathway vesicles. However, the differences in location and expression responses against stresses suggest that their functions are not totally overlapping.

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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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MIA3/TANGO1 enables efficient secretion by constraining COPII vesicle budding

10.1101/2021.02.24.432632 ◽

2021 ◽

Author(s):

Janine McCaughey ◽

Judith M. Mantell ◽

Chris R. Neal ◽

Kate Heesom ◽

David J. Stephens

Keyword(s):

Endoplasmic Reticulum ◽

Light Microscopy ◽

Secretory Pathway ◽

Genome Engineering ◽

High Volume ◽

Vesicle Budding ◽

Early Secretory Pathway ◽

Copii Vesicle ◽

Intermediate Compartment ◽

Golgi Organization

AbstractComplex machinery is required to drive secretory cargo export from the endoplasmic reticulum. In vertebrates, this includes transport and Golgi organization protein 1 (TANGO1), encoded by the Mia3 gene. Here, using genome engineering of human cells light microscopy, secretion assays, and proteomics, we show loss of Mia3/TANGO1 results in formation of numerous vesicles and a loss of early secretory pathway integrity. This restricts secretion not only of large proteins like procollagens but of all types of secretory cargo. Our data shows that Mia3/TANGO1 constrains the propensity of COPII to form vesicles promoting instead the formation of the ER-Golgi intermediate compartment. Thus, Mia3/TANGO1 facilities the secretion of complex and high volume cargoes from vertebrate cells.

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Peroxisomal membrane proteins are properly targeted to peroxisomes in the absence of COPI- and COPII-mediated vesicular transport

Journal of Cell Science ◽

10.1242/jcs.114.11.2199 ◽

2001 ◽

Vol 114 (11) ◽

pp. 2199-2204 ◽

Cited By ~ 1

Author(s):

Tineke Voorn-Brouwer ◽

Astrid Kragt ◽

Henk F. Tabak ◽

Ben Distel

Keyword(s):

Endoplasmic Reticulum ◽

Membrane Proteins ◽

Secretory Pathway ◽

Human Fibroblasts ◽

Vesicle Transport ◽

Peroxisome Biogenesis ◽

Peroxisomal Membrane ◽

Classic Model ◽

Early Secretory Pathway

The classic model for peroxisome biogenesis states that new peroxisomes arise by the fission of pre-existing ones and that peroxisomal matrix and membrane proteins are recruited directly from the cytosol. Recent studies challenge this model and suggest that some peroxisomal membrane proteins might traffic via the endoplasmic reticulum to peroxisomes. We have studied the trafficking in human fibroblasts of three peroxisomal membrane proteins, Pex2p, Pex3p and Pex16p, all of which have been suggested to transit the endoplasmic reticulum before arriving in peroxisomes. Here, we show that targeting of these peroxisomal membrane proteins is not affected by inhibitors of COPI and COPII that block vesicle transport in the early secretory pathway. Moreover, we have obtained no evidence for the presence of these peroxisomal membrane proteins in compartments other than peroxisomes and demonstrate that COPI and COPII inhibitors do not affect peroxisome morphology or integrity. Together, these data fail to provide any evidence for a role of the endoplasmic reticulum in peroxisome biogenesis.

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