Endoplasmic reticulum articles within Nature Communications

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• Article
  24 April 2024 | Open Access

  TANGO1 inhibitors reduce collagen secretion and limit tissue scarring

  Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.

  • Ishier Raote
  • , Ann-Helen Rosendahl
  •  & Vivek Malhotra

• Article
  29 March 2024 | Open Access

  Cholesterol-binding motifs in STING that control endoplasmic reticulum retention mediate anti-tumoral activity of cholesterol-lowering compounds

  Cholesterol lowering medication positively affects anti-cancer immune response, but the underpinning mechanism is not fully known. Here authors show that the effect is mediated by specific cholesterol binding motifs in STING, a key mediator of inflammation, via regulating its trafficking to Golgi.

  • Bao-cun Zhang
  • , Marlene F. Laursen
  •  & Martin R. Jakobsen

• Article
  07 March 2024 | Open Access

  RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling

  Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that primarily responds to ligation of bacterial lipopolysaccharide. Here the authors suggest the intramembrane protease RHBDL4 as a regulator of TLR4 signaling.

  • Julia D. Knopf
  • , Susanne S. Steigleder
  •  & Marius K. Lemberg

• Article
  29 February 2024 | Open Access

  OrthoID: profiling dynamic proteomes through time and space using mutually orthogonal chemical tools

  Proteomics at the organelle contact site remains challenging due to the spatial and temporal dynamics of proteins. Here, the authors developed OrthoID, a mutually orthogonal dual enzymatic proteomics approach to explore the proteome at the contact site of the endoplasmic reticulum and mitochondria.

  • Ara Lee
  • , Gihyun Sung
  •  & Kimoon Kim

• Article
  16 February 2024 | Open Access

  SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex

  The importance of the SEL1L-HRD1 interaction in vivo was unclear. Here, authors reported that SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex by recruiting the E2 enzyme UBE2J1 and DERLIN to HRD1.

  • Liangguang Leo Lin
  • , Huilun Helen Wang
  •  & Ling Qi

• Article
  22 January 2024 | Open Access

  Proteomic screens of SEL1L-HRD1 ER-associated degradation substrates reveal its role in glycosylphosphatidylinositol-anchored protein biogenesis

  The nature of SEL1L-HRD1 ERAD substrates remains unclear. Here, the authors identified ~100 endogenous substrates, and showed that SEL1L-HRD1 ERAD is indispensable for the activity of GPI transamidase complex and the biogenesis of GPI-anchored proteins.

  • Xiaoqiong Wei
  • , You Lu
  •  & Ling Qi

• Article
  15 December 2023 | Open Access

  The function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways

  Berkane et al. investigated the activation process of selective autophagy of the ER. They show that that phosphorylation of FAM134 proteins by CK2 is a prerequisite for the formation of large micro-clusters of high-density at the ER membrane.

  • Rayene Berkane
  • , Hung Ho-Xuan
  •  & Alexandra Stolz

• Article
  08 November 2023 | Open Access

  Spatially resolved mapping of proteome turnover dynamics with subcellular precision

  Mapping protein turnover dynamics with subcellular precision is crucial for understanding cell physiology and pathology. Here, the authors leveraged APEX2-mediated proximity labeling to develop prox-SILAC methods to profile protein turnover rates in the mitochondria and endoplasmic reticulum.

  • Feng Yuan
  • , Yi Li
  •  & Peng Zou

• Article
  30 October 2023 | Open Access

  DIAPH1-MFN2 interaction regulates mitochondria-SR/ER contact and modulates ischemic/hypoxic stress

  Proximity between mitochondria and endoplasmic reticulum regulates mitochondria fitness and is adversely affected by tissue ischemia. This work reveals that Diaphanous1-Mitofusin2 interaction regulates this proximity and impairs recovery in ischemia.

  • Gautham Yepuri
  • , Lisa M. Ramirez
  •  & Ravichandran Ramasamy

• Article
  04 October 2023 | Open Access

  Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress

  Endonuclease G is known to translocate to the nucleus during apoptosis, but less is known about its role in the cytosol. Here, the authors show that cytoplasmic endonuclease G activates mTORC2 signaling and ER stress to promote NAFLD in female mice.

  • Wenjun Wang
  • , Junyang Tan
  •  & Qinghua Zhou

• Article
  21 September 2023 | Open Access

  Regulation of cellular cholesterol distribution via non-vesicular lipid transport at ER-Golgi contact sites

  The molecular mechanisms responsible for cellular cholesterol distribution remain unclear. Here, the authors identify a key role of lipid transfer proteins ORP9, OSBP, and GRAMD1s in maintaining cholesterol levels in the Golgi and plasma membrane.

  • Tomoki Naito
  • , Haoning Yang
  •  & Yasunori Saheki

• Article
  25 August 2023 | Open Access

  PINK1 and Parkin regulate IP₃R-mediated ER calcium release

  Loss of two PD genes, PINK1 and Parkin, leads to a robust increase in ER calcium release. Here, the authors show that suppression of IP₃R activity via inhibiting CISD1 is sufficient to rescue the PD-related phenotypes in PINK1 or Parkin null animal models.

  • Su Jin Ham
  • , Heesuk Yoo
  •  & Jongkyeong Chung

• Article
  19 July 2023 | Open Access

  A signal peptide peptidase is required for ER-symbiosome proximal association and protein secretion

  During nitrogen fixing symbiosis, rhizobia enter legume nodule cells to form the symbiosome. Here the authors report that a nodule-specific signal peptide peptidase is essential for the molecular communication between host cells and the symbiont.

  • Jian Yang
  • , Niu Zhai
  •  & Huairong Pan

• Article
  13 June 2023 | Open Access

  TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress

  Researchers reveal how the stress of the endoplasmic reticulum is transmitted to the nuclear envelope, which swells, and is brought back to physiologic shape by autophagic pathways.

  • Marika K. Kucińska
  • , Juliette Fedry
  •  & Maurizio Molinari

• Article
  30 May 2023 | Open Access

  The mechanisms to dispose of misfolded proteins in the endoplasmic reticulum of adipocytes

  Endoplasmic reticulum (ER)-associated degradation (ERAD) and ER-phagy are two central degradative mechanisms in the ER. Here the authors describe the sequence of events underlying the disposition of misfolded ER proteins by ERAD and ER-phagy.

  • Shuangcheng Alivia Wu
  • , Chenchen Shen
  •  & Ling Qi

• Article
  10 May 2023 | Open Access

  Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles

  Virus triggered lipophagy is important for flaviviral assembly and coordinated by Aup1 and the ubiquitin conjugating enzyme E2. Here, Lan et al further characterise the interplay between these proteins and how they function to modulate selective autophagy and viral replication.

  • Yun Lan
  • , Sophie Wilhelmina van Leur
  •  & Sumana Sanyal

• Article
  05 May 2023 | Open Access

  Oligomeric scaffolding for curvature generation by ER tubule-forming proteins

  How membranes are stretched and bent around the complex structures of cellular organelles is not fully understood. Xiang and colleagues report that endoplasmic reticulum tubule-forming proteins generate membrane curvature by constructing a curved oligomeric scaffold.

  • Yun Xiang
  • , Rui Lyu
  •  & Junjie Hu

• Article
  23 March 2023 | Open Access

  The K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper

  In contrast to the current model based on fast recycling of the K/HDEL receptor (ERD2) between the ER and the Golgi apparatus, here authors show evidence that ERD2 is specifically retained in the Golgi apparatus and evades joining its ligands en route to the ER.

  • Jonas C. Alvim
  • , Robert M. Bolt
  •  & Jurgen Denecke

• Article
  17 January 2023 | Open Access

  Dynamics of CLIMP-63 S-acylation control ER morphology

  A key player in the formation of endoplasmic reticulum sheets is CLIMP-63, but mechanistic details remained elusive. Here authors combined cellular experiments and mathematical modelling to show that S-acylation of CLIMP-63 regulates its function by mediating its oligomerisation, turnover, and localisation.

  • Patrick A. Sandoz
  • , Robin A. Denhardt-Eriksson
  •  & F. Gisou van der Goot

• Article
  25 October 2022 | Open Access

  Termination of the unfolded protein response is guided by ER stress-induced HAC1 mRNA nuclear retention

  Chromatin remodeler Isw1 prevents export of maturing ribonucleoprotein particles. Here, the authors show that Isw1 inhibits the Unfolded Protein Response (UPR) from the nucleus by binding and restricting export of the mRNA encoding the main effector of UPR, thereby tuning adaptation to ER stress.

  • Laura Matabishi-Bibi
  • , Drice Challal
  •  & Anna Babour

• Article
  19 October 2022 | Open Access

  The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans

  Endoplasmic reticulum stress activates the unfolded protein response (UPR). The authors show that glucose extends the lifespan of aged animals by activating the otherwise quiescent UPR while causing a UPR-dependent reduced longevity in young animals

  • Caroline Beaudoin-Chabot
  • , Lei Wang
  •  & Guillaume Thibault

• Article
  10 October 2022 | Open Access

  Scleral PERK and ATF6 as targets of myopic axial elongation of mouse eyes

  he underlying mechanism of myopic axial elongation of the eyes has long been unknown. Here, the authors show that endoplasmic reticulum stress in the sclera and its sensor proteins, PERK and ATF6, are involved in myopic axial elongation

  • Shin-ichi Ikeda
  • , Toshihide Kurihara
  •  & Kazuo Tsubota

• Article
  10 August 2022 | Open Access

  Molecular basis of MHC I quality control in the peptide loading complex

  The immune system monitors the health status of cells by surveilling fragments of foreign molecules from invaders presented on MHC I complexes at the cell surface. Here, the authors investigate the sequence of events of MHC I assembly and quality control cycle.

  • Alexander Domnick
  • , Christian Winter
  •  & Robert Tampé

• Article
  28 June 2022 | Open Access

  Structural basis for mitoguardin-2 mediated lipid transport at ER-mitochondrial membrane contact sites

  The ER-mitochondria contact sites are crucial for exchanging phospholipids. Here, Kim et al. present crystal structures of mitoguardin-2 (MIGA2) which reveal that MIGA2 directly binds phospholipids and transfers them between the ER and mitochondria.

  • Hyunwoo Kim
  • , Seowhang Lee
  •  & Changwook Lee

• Article
  19 May 2022 | Open Access

  Shielding of actin by the endoplasmic reticulum impacts nuclear positioning

  The nucleus connects to the actin cytoskeleton for nuclear movement in migrating cells. Here, the authors show that the endoplasmic reticulum shields actin cables to generate asymmetric nucleo-cytoskeleton connections for nuclear positioning.

  • Cátia Silva Janota
  • , Andreia Pinto
  •  & Edgar R. Gomes

• Article
  18 May 2022 | Open Access

  HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins

  RNA binding protein HDLBP (or Vigilin) localizes in the endoplasmic reticulum (ER) membrane. Here the authors show that HDLBP contributes to translation of ER-targeted mRNAs.

  • Ulrike Zinnall
  • , Miha Milek
  •  & Markus Landthaler

• Article
  16 May 2022 | Open Access

  Ca²⁺-mediated higher-order assembly of heterodimers in amino acid transport system b^0,+ biogenesis and cystinuria

  Cystinuria is caused by mutations in heterodimeric amino acid transporter known as system b^0,+. Here, authors discover that Ca²⁺ stabilizes the interface between two system b^0,+ regulatory subunits rBAT, leading to super-dimerization of the b^0,+AT–rBAT heterodimer, facilitating system b^0,+ maturation.

  • Yongchan Lee
  • , Pattama Wiriyasermkul
  •  & Shushi Nagamori

• Article
  06 May 2022 | Open Access

  Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP

  Aggregation of misfolded proteins underlie dementias. Here, the authors show that stressed cells activate an innate mechanism to resolve aggregates of defective proteins in the endoplasmic reticulum, where a third of cellular proteins are produced.

  • Eduardo Pinho Melo
  • , Tasuku Konno
  •  & Edward Avezov

• Article
  24 March 2022 | Open Access

  Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay

  In Drosophila, ER-targeted mRNAs are degraded by Ire1-dependent pathway. Here the authors report that the fly mRNA binding protein Pumilio is phosphorylated by Ire1 and binds to Xbp1 mRNA, protecting it from the non-canonical endoribonuclease activity of Ire1.

  • Fátima Cairrão
  • , Cristiana C. Santos
  •  & Pedro M. Domingos

• Article
  10 March 2022 | Open Access

  iRhom pseudoproteases regulate ER stress-induced cell death through IP₃ receptors and BCL-2

  Cells that cannot cope with persistent endoplasmic reticulum stress will die. Here, the authors show that iRhom pseudoproteases regulate cell death by modulating the ability of BCL-2 to inhibit calcium flow through IP₃R channels.

  • Iqbal Dulloo
  • , Peace Atakpa-Adaji
  •  & Matthew Freeman

• Article
  15 December 2021 | Open Access

  Decoding non-canonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1α

  IRE1 helps mitigate endoplasmic-reticulum stress by cleaving specific mRNAs at a conserved sequence endomotif via regulated IRE1-dependent decay (RIDD). Here the authors discover a more promiscuous IRE1 activity dubbed RIDD lacking endomotif (RIDDLE).

  • Adrien Le Thomas
  • , Elena Ferri
  •  & Avi Ashkenazi

• Article
  10 December 2021 | Open Access

  Acute RyR1 Ca²⁺ leak enhances NADH-linked mitochondrial respiratory capacity

  Ryanodine receptor type 1 (RyR1) are involved in skeletal muscle contraction. Here, the authors show that a transient calcium leak in response to exercise-induced post translational modifications of RyR1 causes mitochondrial remodeling to improve respiration.

  • Nadège Zanou
  • , Haikel Dridi
  •  & Nicolas Place

• Article
  30 November 2021 | Open Access

  WFS1 functions in ER export of vesicular cargo proteins in pancreatic β-cells

  The role of cargo receptors in proinsulin export from the ER is unclear. Here, the authors identify the WFS1 protein, which is mutated in Wolfram syndrome and associated with diabetes, as an ER to Golgi cargo receptor required for normal insulin processing and secretion.

  • Linlin Wang
  • , Hongyang Liu
  •  & Zonghong Li

• Article
  18 October 2021 | Open Access

  PDZD-8 and TEX-2 regulate endosomal PI(4,5)P₂ homeostasis via lipid transport to promote embryogenesis in C. elegans

  Cellular membranes have distinct lipid compositions despite intermixing, and it is unclear why plasma membrane lipids do not accumulate on endosomes. Here, the authors use the C. elegans embryo to identify lipid transfer proteins and phosphatases that are critical for endosomal lipid homeostasis.

  • Darshini Jeyasimman
  • , Bilge Ercan
  •  & Yasunori Saheki

• Article
  13 October 2021 | Open Access

  PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones

  Degradation of misfolded proteins from the endoplasmic reticulum (ER) is important for maintaining proper cellular protein homeostasis. Here, the authors discovered that the ER membrane protein PGRMC1 binds to misfolded prohormones for recruitment into the ER-phagy degradative pathway.

  • Yu-Jie Chen
  • , Jeffrey Knupp
  •  & Billy Tsai

• Article
  08 October 2021 | Open Access

  Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex

  Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.

  • Yoel A. Klug
  • , Justin C. Deme
  •  & Pedro Carvalho

• Article
  18 August 2021 | Open Access

  Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD

  The ER chaperone BiP is regulated by FICD-mediated AMPylation and deAMPylation. Here, the authors characterise the structure of mammalian AMPylated BiP bound to FICD, by X-ray crystallography and neutron scattering, providing insights into the mechanism of BiP AMPylation and deAMPylation.

  • Luke A. Perera
  • , Steffen Preissler
  •  & David Ron

• Article
  12 August 2021 | Open Access

  Interferon lambda 4 impairs hepatitis C viral antigen presentation and attenuates T cell responses

  A genetic variant in the IFN-lambda 4 gene has been associated with poor hepatitis C virus prognosis but it is not clear how this functions. Here the authors show that IFN-lambda 4 promotes ER stress and inhibits presentation of HCV epitopes to CD8⁺ T cells.

  • Qian Chen
  • , Mairene Coto-Llerena
  •  & Markus H. Heim

• Article
  27 July 2021 | Open Access

  SNX19 restricts endolysosome motility through contacts with the endoplasmic reticulum

  Endoplasmic reticulum (ER)-interorganelle membrane contact sites have emerged as key regulators of organelle dynamics. Here, the authors report that the ER-resident protein SNX19 mediates ER-endolysosome membrane contacts to maintain the perinuclear distribution of endolysosomes and restrict their motility.

  • Amra Saric
  • , Spencer A. Freeman
  •  & Juan S. Bonifacino

• Article
  23 July 2021 | Open Access

  KRAP tethers IP₃ receptors to actin and licenses them to evoke cytosolic Ca²⁺ signals

  Calcium signals initiated by IP3 receptors in ER membranes regulate most cellular activities. Here, the authors show that KRas-induced actininteracting protein (KRAP) tethers a small subset of IP3 receptors to actin and licenses them to evoke cytosolic calcium signals.

  • Nagendra Babu Thillaiappan
  • , Holly A. Smith
  •  & Colin W. Taylor

• Article
  08 June 2021 | Open Access

  Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites

  Membrane contact sites (MCS) are subcellular regions where two organelles appose their membranes to exchange small molecules, including lipids. Here authors designed an in vitro MCS suitable for cryotomography and sub-tomogram analysis which sheds light on the recruitment of proteins of different sizes within MCS of adjustable thickness.

  • Eugenio de la Mora
  • , Manuela Dezi
  •  & Daniel Lévy

• Article
  10 May 2021 | Open Access

  FUNDC1-dependent mitochondria-associated endoplasmic reticulum membranes are involved in angiogenesis and neoangiogenesis

  Mitochondria-associated ER membranes (MAMs) are involved in the regulation of many cellular functions. Here, the authors report that FUNDC1-dependent mitochondria-associated endoplasmic reticulum membranes play an essential role in the process of angiogenesis and neoangiogenesis.

  • Cheng Wang
  • , Xiaoyan Dai
  •  & Kai Huang

• Article
  06 April 2021 | Open Access

  A slowly cleaved viral signal peptide acts as a protein-integral immune evasion domain

  Glycoprotein US9 of human cytomegalovirus downregulates the activating immune ligand MICA*008 to avoid NK cell activation. Here, Seidel et al. show that the signal peptide of US9 is cleaved unusually slowly, causing MICA*008 to be retained in the endoplasmic reticulum (ER) and degraded via the ER quality control system.

  • Einat Seidel
  • , Liat Dassa
  •  & Ofer Mandelboim

• Article
  23 February 2021 | Open Access

  Facilitative lysosomal transport of bile acids alleviates ER stress in mouse hematopoietic precursors

  Mutations in ENT3, encoded by SLC29A3, result in anaemia and erythroid hypoplasia, suggesting roles in erythropoiesis. Here the authors show that ENT3 acts as a lysosomal bile acid transporter, and mutation compromises taurine conjugated bile acid transport in erythroid progenitors leading to ER stress, and anaemia.

  • Avinash K. Persaud
  • , Sreenath Nair
  •  & Rajgopal Govindarajan

• Article
  25 January 2021 | Open Access

  Mechanism of membrane-curvature generation by ER-tubule shaping proteins

  The endoplasmic reticulum network consists of tubules with high membrane curvature in cross-section, generated by the reticulons and REEPs, but how they introduce curvature is poorly understood. Here authors show that REEPs form homodimers and use their amphipathic helix and trans-membrane segments to introduce high membrane curvature that can even lead to the formation of lipoprotein particles.

  • Ning Wang
  • , Lindsay D. Clark
  •  & Tom A. Rapoport

• Article
  14 December 2020 | Open Access

  Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands

  The RNase activity of Inositol-Requiring Enzyme 1 (IRE1) can be allosterically regulated by ATP-competitive inhibitors of the IRE1 kinase domain. Here, the authors identify ATP-competitive IRE1 RNase activators with improved selectivity and cellular activity, and elucidate their mechanism of action.

  • Elena Ferri
  • , Adrien Le Thomas
  •  & Weiru Wang

• Article
  02 November 2020 | Open Access

  Armadillo-repeat kinesin1 interacts with Arabidopsis atlastin RHD3 to move ER with plus-end of microtubules

  The architecture of the endoplasmic reticulum (ER) is shaped by both atlastin GTPases and the cytoskeleton. Here the authors show that ARK1, an armadillo repeat kinesin, interacts with the Arabidopsis atlastin RHD3 to guide ER tubule fusions via microtubules to generate a fine ER network.

  • Jiaqi Sun
  • , Mi Zhang
  •  & Huanquan Zheng

• Article
  20 July 2020 | Open Access

  PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria

  Membrane contact sites between organelles have been shown to play important biological roles. Here, the authors show that at the ER, PDZD8 associates with Protrudin and also with Rab7 endosomes and recruits mitochondria to form three-way contacts.

  • Yael Elbaz-Alon
  • , Yuting Guo
  •  & Jodi Nunnari

• Article
  03 July 2020 | Open Access

  Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at contacts with forming autophagosomal membranes

  The ER is subject to autophagy (ER-phagy) for turnover, with Atg40 acting as a receptor to sequester ER with Atg8 in autophagosomes. Here, the authors show that Atg40 is clustered by interaction with Atg8 to generate local membrane curvature and promote autophagosome packing.

  • Keisuke Mochida
  • , Akinori Yamasaki
  •  & Hitoshi Nakatogawa

• Article
  03 July 2020 | Open Access

  TMEM16K is an interorganelle regulator of endosomal sorting

  The endolysosomal pathway plays an important role in regulating protein and lipid sorting and degradation. Here, the authors show that TMEM16K, an endoplasmic reticulum lipid scramblase, forms ER-endosome contact sites where it regulates endosomal sorting.

  • Maja Petkovic
  • , Juan Oses-Prieto
  •  & Yuh Nung Jan