Insertion of tail-anchored proteins into the endoplasmic reticulum membrane

2019 ◽  
Vol 68 ◽  
Author(s):  
Evelina DeLaurentis ◽  
Akos Farkas ◽  
Blanche Schwappach
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Membrane

scholarly journals Alternative redox forms of ASNA-1 separate insulin signaling from tail-anchored protein targeting and cisplatin resistance in C. elegans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dorota Raj ◽  
Ola Billing ◽  
Agnieszka Podraza-Farhanieh ◽  
Bashar Kraish ◽  
Oskar Hemmingsson ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Insulin Secretion ◽  
Protein Targeting ◽  
Cisplatin Resistance ◽  
Acquired Resistance ◽  
Endoplasmic Reticulum Membrane ◽  
C Elegans ◽  
Cisplatin Sensitivity ◽  
Tumor Environment ◽  
The One

AbstractCisplatin is a frontline cancer therapeutic, but intrinsic or acquired resistance is common. We previously showed that cisplatin sensitivity can be achieved by inactivation of ASNA-1/TRC40 in mammalian cancer cells and in Caenorhabditis elegans. ASNA-1 has two more conserved functions: in promoting tail-anchored protein (TAP) targeting to the endoplasmic reticulum membrane and in promoting insulin secretion. However, the relation between its different functions has remained unknown. Here, we show that ASNA-1 exists in two redox states that promote TAP-targeting and insulin secretion separately. The reduced state is the one required for cisplatin resistance: an ASNA-1 point mutant, in which the protein preferentially was found in the oxidized state, was sensitive to cisplatin and defective for TAP targeting but had no insulin secretion defect. The same was true for mutants in wrb-1, which we identify as the C. elegans homolog of WRB, the ASNA1/TRC40 receptor. Finally, we uncover a previously unknown action of cisplatin induced reactive oxygen species: cisplatin induced ROS drives ASNA-1 into the oxidized form, and selectively prevents an ASNA-1-dependent TAP substrate from reaching the endoplasmic reticulum. Our work suggests that ASNA-1 acts as a redox-sensitive target for cisplatin cytotoxicity and that cisplatin resistance is likely mediated by ASNA-1-dependent TAP substrates. Treatments that promote an oxidizing tumor environment should be explored as possible means to combat cisplatin resistance.

scholarly journals Ceramide chain length–dependent protein sorting into selective endoplasmic reticulum exit sites

2020 ◽  
Vol 6 (50) ◽  
pp. eaba8237
Author(s):  
Sofia Rodriguez-Gallardo ◽  
Kazuo Kurokawa ◽  
Susana Sabido-Bozo ◽  
Alejandro Cortes-Gomez ◽  
Atsuko Ikeda ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Chain Length ◽  
Secretory Pathway ◽  
Protein Sorting ◽  
Endoplasmic Reticulum Membrane ◽  
Lipid Chain ◽  
Secretory Transport ◽  
Dependent Protein ◽  
Cellular Compartmentalization

Protein sorting in the secretory pathway is crucial to maintain cellular compartmentalization and homeostasis. In addition to coat-mediated sorting, the role of lipids in driving protein sorting during secretory transport is a longstanding fundamental question that still remains unanswered. Here, we conduct 3D simultaneous multicolor high-resolution live imaging to demonstrate in vivo that newly synthesized glycosylphosphatidylinositol-anchored proteins having a very long chain ceramide lipid moiety are clustered and sorted into specialized endoplasmic reticulum exit sites that are distinct from those used by transmembrane proteins. Furthermore, we show that the chain length of ceramide in the endoplasmic reticulum membrane is critical for this sorting selectivity. Our study provides the first direct in vivo evidence for lipid chain length–based protein cargo sorting into selective export sites of the secretory pathway.

Stop-and-Move of a Marginally Hydrophobic Segment Translocating across the Endoplasmic Reticulum Membrane

2013 ◽  
Vol 425 (17) ◽  
pp. 3205-3216 ◽  
Author(s):  
Yukiko Onishi ◽  
Marifu Yamagishi ◽  
Kenta Imai ◽  
Hidenobu Fujita ◽  
Yuichiro Kida ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Membrane

Secretory proteins move through the endoplasmic reticulum membrane via an aqueous, gated pore

Cell ◽  
1994 ◽  
Vol 78 (3) ◽  
pp. 461-471 ◽  
Author(s):  
Kathleen S. Crowley ◽  
Shuren Liao ◽  
Veronica E. Worrell ◽  
Gregory D. Reinhart ◽  
Arthur E. Johnson
Keyword(s):  
Endoplasmic Reticulum ◽  
Secretory Proteins ◽  
Endoplasmic Reticulum Membrane

scholarly journals The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane.

1997 ◽  
Vol 8 (9) ◽  
pp. 1805-1814 ◽  
Author(s):  
J S Cox ◽  
R E Chapman ◽  
P Walter
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Lipid Synthesis ◽  
Secretory Proteins ◽  
Endoplasmic Reticulum Membrane ◽  
Yeast Saccharomyces Cerevisiae ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

The endoplasmic reticulum (ER) is a multifunctional organelle responsible for production of both lumenal and membrane components of secretory pathway compartments. Secretory proteins are folded, processed, and sorted in the ER lumen and lipid synthesis occurs on the ER membrane itself. In the yeast Saccharomyces cerevisiae, synthesis of ER components is highly regulated: the ER-resident proteins by the unfolded protein response and membrane lipid synthesis by the inositol response. We demonstrate that these two responses are intimately linked, forming different branches of the same pathway. Furthermore, we present evidence indicating that this coordinate regulation plays a role in ER biogenesis.

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