A Flat Protein Complex Shapes Rough ER Membrane Sheets

Sawyer, Eric M.; Jensen, Liv E.; Meehl, Janet B.; Larsen, Kevin P.; Petito, Daniel A.; Hurley, James H.; Voeltz, Gia K.

doi:10.1101/2023.10.06.559866

Cited by 2 publications

(3 citation statements)

References 53 publications

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“…However, the mechanisms underlying S1R multifunctionality have yet to be clarified. Understanding the structural kinetics of S1R, which are known to be related to its function [ 27 , 28 ], would improve our understanding of S1R and may extend the already wide range of S1R therapeutic use. In this study we first established models wherein agonists induce monomerization, even with in-vivo mice models, which corroborate previous results from cellular models [ 29 – 31 ] (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…observe that S1R mutations of amino acids contained in the domains, highlighted in Fig. 5 , decrease S1R oligomerization and impact rough ER shaping [ 28 ]. More experiments are needed to determine the exact consequences of S1R structural changes on S1R’s effects on cell survival.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover the transmembrane domain, located on the N-terminal, seems also to contain a cholesterol-binding motif [ 17 ]. Despite recent publications demonstrating that the structure of S1R could affect its antiviral function [ 27 ] or its ability to shape ER membrane [ 28 ], the relationship between S1R structure and function is not yet totally clear. At resting state S1R is found as monomers and homomers [ 29 ], and upon activation S1R seems to tend toward monomeric conformation [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Benzomorphan and non-benzomorphan agonists differentially alter sigma-1 receptor quaternary structure, as does types of cellular stress

Couly,

Yasui,

Foncham

et al. 2024

Cell. Mol. Life Sci.

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Sigma-1 receptor (S1R) is a calcium-sensitive, ligand-operated receptor chaperone present on the endoplasmic reticulum (ER) membrane. S1R plays an important role in ER-mitochondrial inter-organelle calcium signaling and cell survival. S1R and its agonists confer resilience against various neurodegenerative diseases; however, the molecular mechanism of S1R is not yet fully understood. At resting state, S1R is either in a monomeric or oligomeric state but the ratio of these concentrations seems to change upon activation of S1R. S1R is activated by either cellular stress, such as ER-calcium depletion, or ligands. While the effect of ligands on S1R quaternary structure remains unclear, the effect of cellular stress has not been studied. In this study we utilize cellular and an in-vivo model to study changes in quaternary structure of S1R upon activation. We incubated cells with cellular stressors (H2O2 and thapsigargin) or exogenous ligands, then quantified monomeric and oligomeric forms. We observed that benzomorphan-based S1R agonists induce monomerization of S1R and decrease oligomerization, which was confirmed in the liver tissue of mice injected with (+)-Pentazocine. Antagonists block this effect but do not induce any changes when used alone. Oxidative stress (H2O2) increases the monomeric/oligomeric S1R ratio whereas ER calcium depletion (thapsigargin) has no effect. We also analyzed the oligomerization ability of various truncated S1R fragments and identified the fragments favorizing oligomerization. In this publication we demonstrate that quaternary structural changes differ according to the mechanism of S1R activation. Therefore, we offer a novel perspective on S1R activation as a nuanced phenomenon dependent on the type of stimulus.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Benzomorphan and non-benzomorphan agonists differentially alter sigma-1 receptor quaternary structure, as does types of cellular stress

Couly,

Yasui,

Foncham

et al. 2024

Cell. Mol. Life Sci.

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Sculpting nuclear envelope identity from the endoplasmic reticulum during the cell cycle

Deolal,

Scholz,

Ren

et al. 2024

Nucleus

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The nuclear envelope (NE) regulates nuclear functions, including transcription, nucleocytoplasmic transport, and protein quality control. While the outer membrane of the NE is directly continuous with the endoplasmic reticulum (ER), the NE has an overall distinct protein composition from the ER, which is crucial for its functions. During open mitosis in higher eukaryotes, the NE disassembles during mitotic entry and then reforms as a functional territory at the end of mitosis to reestablish nucleocytoplasmic compartmentalization. In this review, we examine the known mechanisms by which the functional NE reconstitutes from the mitotic ER in the continuous ER–NE endomembrane system during open mitosis. Furthermore, based on recent findings indicating that the NE possesses unique lipid metabolism and quality control mechanisms distinct from those of the ER, we explore the maintenance of NE identity and homeostasis during interphase. We also highlight the potential significance of membrane junctions between the ER and NE.

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A Flat Protein Complex Shapes Rough ER Membrane Sheets

Cited by 2 publications

References 53 publications

Benzomorphan and non-benzomorphan agonists differentially alter sigma-1 receptor quaternary structure, as does types of cellular stress

Benzomorphan and non-benzomorphan agonists differentially alter sigma-1 receptor quaternary structure, as does types of cellular stress

Sculpting nuclear envelope identity from the endoplasmic reticulum during the cell cycle

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