A CTDNEP 1-Lipin 1-mTOR Regulatory Network Restricts ER Membrane Biogenesis to Enable Chromosome Motions Necessary for Mitotic Fidelity

2021 ◽  
Author(s):  
Holly Merta ◽  
Jake W. Carrasquillo Rodriguez ◽  
Maya I. Anjur-Dietrich ◽  
Mitchell E. Granade ◽  
Tevis Vitale ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Membrane Biogenesis ◽  
Lipin 1 ◽  
Er Membrane

scholarly journals A CTDNEP1-lipin 1-mTOR regulatory network restricts ER membrane biogenesis to enable chromosome motions necessary for mitotic fidelity

2021 ◽  
Author(s):  
Holly Merta ◽  
Jake W. Carrasquillo Rodríguez ◽  
Maya I. Anjur-Dietrich ◽  
Mitchell E. Granade ◽  
Tevis Vitale ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Mitotic Chromosome ◽  
Lipid Synthesis ◽  
Membrane Biogenesis ◽  
Mitotic Progression ◽  
Potential Source ◽  
Spindle Disassembly ◽  
Lipin 1 ◽  
Chromosome Movements ◽  
Er Membrane

SummaryThe endoplasmic reticulum (ER) dramatically restructures in open mitosis to become excluded from the mitotic spindle; however, the significance of ER reorganization to mitotic progression is not known. Here, we demonstrate that limiting ER membrane biogenesis enables mitotic chromosome movements necessary for chromosome biorientation and prevention of micronuclei formation. Aberrantly expanded ER membranes increase the effective viscosity of the mitotic cytoplasm to physically restrict chromosome dynamics – slowed chromosome motions impede correction of mitotic errors induced by transient spindle disassembly, leading to severe micronucleation. We define the mechanistic link between regulation of ER membrane biogenesis and mitotic fidelity by demonstrating that a CTDNEP1-lipin 1-mTOR regulatory network limits ER lipid synthesis to prevent chromosome missegregation. Together, this work shows that ER membranes reorganize in mitosis to enable chromosome movements necessary for mitotic error correction and reveal dysregulated lipid metabolism as a potential source of aneuploidy in cancer cells.

Cell cycle regulation of ER membrane biogenesis protects against chromosome missegregation

2021 ◽  
Author(s):  
Holly Merta ◽  
Jake W. Carrasquillo Rodríguez ◽  
Maya I. Anjur-Dietrich ◽  
Tevis Vitale ◽  
Mitchell E. Granade ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Membrane Biogenesis ◽  
Chromosome Missegregation ◽  
Cycle Regulation ◽  
Er Membrane

scholarly journals Control of endoplasmic reticulum membrane biogenesis by regulators of lipid metabolism

2020 ◽  
Author(s):  
Peter W. Bircham ◽  
Dimitrios Papagiannidis ◽  
Christian Lüchtenborg ◽  
Giulia Ruffini ◽  
Britta Brügger ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Transcriptional Control ◽  
Transmembrane Protein ◽  
Lipid Synthesis ◽  
Endoplasmic Reticulum Membrane ◽  
Membrane Biogenesis ◽  
Storage Lipids ◽  
The Unfolded Protein Response ◽  
Er Membrane

ABSTRACTCells dynamically adapt organelle size to current physiological demand. Organelle growth and proliferation require membrane biogenesis and need to be coordinated with lipid metabolism. The endoplasmic reticulum (ER) can undergo massive expansion but the mechanisms that govern ER membrane biogenesis are unclear. Here, we genetically screen for factors mediating ER expansion in budding yeast and identify lipid synthesis enzymes and the ER transmembrane protein Ice2 as strong hits. Ice2 inhibits the conserved phosphatidic acid phosphatase Pah1 by opposing the activity of the Nem1-Spo7 complex. This regulation counteracts the production of storage lipids and directs lipid metabolism towards membrane biogenesis. Furthermore, Ice2 acts in concert with the transcriptional control of lipid synthesis enzymes and cooperates with the unfolded protein response to maintain ER homeostasis. These findings establish the regulation of the lipin ortholog Pah1 as a key determinant of ER membrane biogenesis.

scholarly journals Ice2 promotes ER membrane biogenesis in yeast by inhibiting the conserved lipin phosphatase complex

2021 ◽  
Author(s):  
Dimitrios Papagiannidis ◽  
Peter W Bircham ◽  
Christian Lüchtenborg ◽  
Oliver Pajonk ◽  
Giulia Ruffini ◽  
...  
Keyword(s):  
Membrane Biogenesis ◽  
Er Membrane

scholarly journals The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1

2013 ◽  
Vol 2 (1) ◽  
pp. 38-46 ◽  
Author(s):  
M.F. Michelle Sim ◽  
Rowena J. Dennis ◽  
Evelyne M. Aubry ◽  
Nardev Ramanathan ◽  
Hiroshi Sembongi ◽  
...  
Keyword(s):  
Lipin 1 ◽  
Er Membrane

TMCC3 localizes at the three-way junctions for the proper tubular network of the endoplasmic reticulum

2019 ◽  
Vol 476 (21) ◽  
pp. 3241-3260
Author(s):  
Sindhu Wisesa ◽  
Yasunori Yamamoto ◽  
Toshiaki Sakisaka
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Mammalian Cells ◽  
Coiled Coil ◽  
Transmembrane Domains ◽  
Domain Family ◽  
Coiled Coil Domain ◽  
U2os Cells ◽  
Er Membrane

The tubular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions. Two classes of the conserved ER membrane proteins, atlastins and lunapark, have been shown to reside at the three-way junctions so far and be involved in the generation and stabilization of the three-way junctions. In this study, we report TMCC3 (transmembrane and coiled-coil domain family 3), a member of the TEX28 family, as another ER membrane protein that resides at the three-way junctions in mammalian cells. When the TEX28 family members were transfected into U2OS cells, TMCC3 specifically localized at the three-way junctions in the peripheral ER. TMCC3 bound to atlastins through the C-terminal transmembrane domains. A TMCC3 mutant lacking the N-terminal coiled-coil domain abolished localization to the three-way junctions, suggesting that TMCC3 localized independently of binding to atlastins. TMCC3 knockdown caused a decrease in the number of three-way junctions and expansion of ER sheets, leading to a reduction of the tubular ER network in U2OS cells. The TMCC3 knockdown phenotype was partially rescued by the overexpression of atlastin-2, suggesting that TMCC3 knockdown would decrease the activity of atlastins. These results indicate that TMCC3 localizes at the three-way junctions for the proper tubular ER network.

Construction of transcription factor mutual regulatory network based on a new database

2014 ◽  
Author(s):  
Zhenping Yang ◽  
Wei Wang ◽  
Yang Yang ◽  
Hongfei Chen ◽  
Jinke Wang
Keyword(s):  
Transcription Factor ◽  
Regulatory Network

Spatial localization of unknown proteins in the endoplasmic reticulum predicts functions

2007 ◽  
Vol 30 (4) ◽  
pp. 84
Author(s):  
Michael D. Jain ◽  
Hisao Nagaya ◽  
Annalyn Gilchrist ◽  
Miroslaw Cygler ◽  
John J.M. Bergeron
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Protein Synthesis ◽  
Protein Function ◽  
Protein Translocation ◽  
Spatial Localization ◽  
Predict Protein Function ◽  
Insight Into ◽  
Soluble Fractions ◽  
Er Membrane

Protein synthesis, folding and degradation functions are spatially segregated in the endoplasmic reticulum (ER) with respect to the membrane and the ribosome (rough and smooth ER). Interrogation of a proteomics resource characterizing rough and smooth ER membranes subfractionated into cytosolic, membrane, and soluble fractions gives a spatial map of known proteins involved in ER function. The spatial localization of 224 identified unknown proteins in the ER is predicted to give insight into their function. Here we provide evidence that the proteomics resource accurately predicts the function of new proteins involved in protein synthesis (nudilin), protein translocation across the ER membrane (nicalin), co-translational protein folding (stexin), and distal protein folding in the lumen of the ER (erlin-1, TMX2). Proteomics provides the spatial localization of proteins and can be used to accurately predict protein function.

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