Phospholipids articles within Nature Communications

Featured

• Article
  20 March 2024 | Open Access

  Rab GTPases and phosphoinositides fine-tune SNAREs dependent targeting specificity of intracellular vesicle traffic

  Targeting of transport vesicles requires specific proteins and membrane lipids. Here, authors microinjected liposomes with a predetermined composition to show that targeting by SNAREs is refined when polyphosphoinositides and Rab GTPases are included.

  • Seiichi Koike
  •  & Reinhard Jahn

• Article
  12 February 2024 | Open Access

  Liquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection

  The authors display the bottom-up design, assembly, and in-depth characterization of defined lipid-RNA structures in the core of lipid nanoparticles. The inverted structures are thermostable and provide better transfection over lamellar structures.

  • Roy Pattipeiluhu
  • , Ye Zeng
  •  & Thomas H. Sharp

• Article
  03 February 2024 | Open Access

  Phosphoglycerate kinase 1 acts as a cargo adaptor to promote EGFR transport to the lysosome

  The epidermal growth factor receptor (EGFR) plays important roles in cell growth and motility. Here, authors reveal an unexpected function for a metabolic enzyme PGK1 and advance the mechanistic understanding of lysosomal transport of EGFR.

  • Shao-Ling Chu
  • , Jia-Rong Huang
  •  & Jia-Wei Hsu

• Article
  04 January 2024 | Open Access

  The juxtamembrane linker of synaptotagmin 1 regulates Ca²⁺ binding via liquid-liquid phase separation

  Synaptotagmin (syt) 1 is a calcium sensor for neuronal exocytosis. Here, the authors show that the juxtamembrane linker of this integral membrane protein negatively regulates its calcium sensing activity by mediating self-association via liquid-liquid phase separation.

  • Nikunj Mehta
  • , Sayantan Mondal
  •  & Edwin R. Chapman

• Article
  13 December 2023 | Open Access

  Molecular mechanism of phospholipid transport at the bacterial outer membrane interface

  Maintenance of lipid asymmetry in the bacterial outer membrane (OM) is mediated by the OmpC-Mla system, but mechanistic details remain to be elucidated. Here, the authors show that electrostatic interactions, conformational dynamics, and membrane thinning may facilitate spontaneous retrograde phospholipid transfer at the OM.

  • Jiang Yeow
  • , Min Luo
  •  & Shu-Sin Chng

• Article
  30 November 2023 | Open Access

  Skeletal muscle-secreted DLPC orchestrates systemic energy homeostasis by enhancing adipose browning

  MyoD is a transcription factor expressed in skeletal muscle that plays a critical role in determining myogenic cell fate. Here, Hu et al. reveal a metabolic role of MyoD in orchestrating systemic energy homeostasis by mediating muscle-fat crosstalk through the muscle-secreted lipokine DLPC.

  • Xiaodi Hu
  • , Mingwei Sun
  •  & Dahai Zhu

• Article
  18 November 2023 | Open Access

  Activation and substrate specificity of the human P4-ATPase ATP8B1

  Asymmetric phospholipid distribution in cell membranes is vital for cellular function. Here, authors reveal how ATP8B1, a P4-ATPase, can transport different lipids, including phosphatidylinositol.

  • Thibaud Dieudonné
  • , Felix Kümmerer
  •  & Poul Nissen

• Article
  23 October 2023 | Open Access

  Acylation of glycerolipids in mycobacteria

  This paper reports on two mycobacterial glycerolipid acyltransferases capable of transferring acyl chains to position 1 or position 2 of both glycerol-3-phosphate and lysophosphatidic acid.

  • Shiva Kumar Angala
  • , Ana Carreras-Gonzalez
  •  & Mary Jackson

• 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
  17 July 2023 | Open Access

  Restoration of PITPNA in Type 2 diabetic human islets reverses pancreatic beta-cell dysfunction

  Type 2 diabetes (T2D) is characterized by pancreatic beta-cell failure. Here, the authors show restoration of Phosphatidylinositol transfer protein alpha (PITPNA), a mediator of PtdIns-4-phosphate synthesis in the trans-Golgi network, in human T2D islets reverses impaired insulin granule maturation, exocytosis, and ER stress.

  • Yu-Te Yeh
  • , Chandan Sona
  •  & Matthew N. Poy

• Article
  14 June 2023 | Open Access

  The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification

  Wang et al. report a structure for human MBOAT7, the enzyme responsible for remodeling acyl chains of phosphatidylinositol. The structure enabled the identification of MBOAT7 inhibitors and provides insights into substrate specificity among MBOATs.

  • Kun Wang
  • , Chia-Wei Lee
  •  & Robert V. Farese Jr

• Article
  13 May 2023 | Open Access

  Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis

  CDP-alcohol phosphatidyltransferase (CDP-AP) is a family of membrane-embedded enzymes that synthesize phospholipids. The authors report structural and functional studies of a eukaryotic CDP-AP and reveal a catalytic center and structural fold different from these of prokaryotic homologs.

  • Lie Wang
  •  & Ming Zhou

• Article
  03 May 2023 | Open Access

  Structural basis for catalysis of human choline/ethanolamine phosphotransferase 1

  Choline/ethanolamine phosphotransferase 1 (CEPT1) catalyzes the last step of the biosynthesis of PC and PE. Here, the authors present the cryo-EM structures of human CEPT1 and its complex with CDP-choline and reveal a hydrophobic chamber to accommodate the acyl tails during the catalytic process.

  • Zhenhua Wang
  • , Meng Yang
  •  & Hongwu Qian

• Article
  17 April 2023 | Open Access

  Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis

  Cancer cells can be dependent on mitochondrial respiration to survive. Here, in pancreatic cancer cells, the authors show that monounsaturated fatty acids-linked ether lipids maintain mitochondrial redox homeostasis and modulate sensitivity to inhibition to electron transport chain complex I.

  • Ziheng Chen
  • , I-Lin Ho
  •  & Haoqiang Ying

• Article
  20 March 2023 | Open Access

  High-resolution separation of bioisomers using ion cloud profiling

  Ion mobility is used in mass spectrometers for structure analysis of biomolecules. Here, the authors show that ion mobility analysis in an ion trap under ultra-high fields enables isomer separation at resolutions over 10,000, wich they demonstrate for isomers of disaccharides, phospholipids, and peptides.

  • Xiaoyu Zhou
  • , Zhuofan Wang
  •  & Zheng Ouyang

• Article
  14 October 2022 | Open Access

  TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis

  The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis.

  • Kasparas Petkevicius
  • , Henrik Palmgren
  •  & Xiao-Rong Peng

• 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
  11 May 2022 | Open Access

  TMEM16 scramblases thin the membrane to enable lipid scrambling

  Lipid scrambling is required for many cellular processes but the lipid-protein interactions that occur during transport are unknown. Using cryoEM and biochemical assays the authors show that membrane thinning is critical for lipid flipping.

  • Maria E. Falzone
  • , Zhang Feng
  •  & Alessio Accardi

• Article
  08 February 2022 | Open Access

  Giant sponge grounds of Central Arctic seamounts are associated with extinct seep life

  This study reports the discovery of dense sponge gardens across the peaks of permanently ice-covered, extinct volcanic seamounts of the Langseth Ridge and on the remnants of a now extinct seep ecosystem. Using approaches to sample and infer food and energy sources to this ice-covered community, the authors suggest that the sponges use refractory organic matter trapped in the extinct seep community on which they sit.

  • T. M. Morganti
  • , B. M. Slaby
  •  & A. Boetius

• Article
  08 February 2022 | Open Access

  Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate

  Liu et al. report structures of human sphingosine 1-phosphate (S1P) receptor 1 (S1P₁) in complex with Gi and S1P or the multiple sclerosis (MS) drug Siponimod, as well as human lysophosphatidic acid (LPA) receptor 1 (LPA₁) in complex with Gi and LPA, revealing distinct conformations of the lysophospholipids interacting with their cognate GPCRs.

  • Shian Liu
  • , Navid Paknejad
  •  & Xin-Yun Huang

• Article
  10 January 2022 | Open Access

  A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their disease-associated regulation

  Different phosphoinositide isomers are involved in a variety of physiological and pathological processes. Here, the authors combine chiral column chromatography and mass spectrometry to measure phosphoinositide regioisomers, revealing their dynamic changes in intra- and extracellular cancer cell milieus.

  • Shin Morioka
  • , Hiroki Nakanishi
  •  & Takehiko Sasaki

• Article
  25 November 2021 | Open Access

  AGPAT2 interaction with CDP-diacylglycerol synthases promotes the flux of fatty acids through the CDP-diacylglycerol pathway

  AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the synthesis of all glycerolipids. Here, the authors show that AGPAT2 and CDP-DAG synthases (CDS1 and CDS2) form functional complexes that promote further conversion of PA along the CDP-DAG pathway of phospholipid synthesis.

  • Hoi Yin Mak
  • , Qian Ouyang
  •  & Hongyuan Yang

• Article
  25 November 2021 | Open Access

  The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3

  During phosphatidylcholine (PC) remodeling re-acylation is catalyzed by lysophosphatidylcholine acyltransferases (LPCAT). Here, the authors present crystal and cryo-EM structures of chicken LPCAT3 in the apo-, acyl donor-bound and acyl receptor-bound states, and based on the structures and further functional analysis they discuss the mechanism of the enzyme.

  • Qing Zhang
  • , Deqiang Yao
  •  & Yu Cao

• Article
  03 November 2021 | Open Access

  Structural library and visualization of endogenously oxidized phosphatidylcholines using mass spectrometry-based techniques

  Oxidized phosphatidylcholines (oxPCs) are a structurally diverse class of lipids associated with various diseases. Here, the authors use mass spectrometry to construct a spectral library of 465 oxPCs and subsequently profile oxPCs formed during acetaminophen-induced acute liver failure in mice.

  • Yuta Matsuoka
  • , Masatomo Takahashi
  •  & Ken-ichi Yamada

• 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
  15 July 2021 | Open Access

  Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins

  Pleckstrin homology (PH) domains are presumed to bind phosphoinositides (PIPs) but only few specific interactions are known. Using TIRF microscopy based assays, functional studies and an experimentally validated prediction algorithm, the authors show that specific PIP binding is widespread among human PH domains.

  • Nilmani Singh
  • , Adriana Reyes-Ordoñez
  •  & Jie Chen

• Article
  22 June 2021 | Open Access

  Structural basis of substrate recognition and translocation by human ABCA4

  Here, cryo-EM structures of human retinal ABCA4 transporter, either in apo state, in complex with ATP or with the physiological lipid substrate N-retinylidene-phosphatidylethanolamine (NRPE), reveal lateral opening, substrate recognition and suggest ‘lateral access and extrusion’ mechanism for ABCA-mediated lipid transport.

  • Tian Xie
  • , Zike Zhang
  •  & Xin Gong

• Article
  20 April 2021 | Open Access

  Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism

  The ventromedial hypothalamus regulates systemic glucose metabolism. Here the authors show that cytosolic phospholipase A2 mediated phospholipid metabolism contributes to this regulation in healthy animals but exert deteriorating effects on glucose homeostasis under high-fat-diet feeding.

  • Ming-Liang Lee
  • , Hirokazu Matsunaga
  •  & Chitoku Toda

• Article
  15 March 2021 | Open Access

  Engineering motile aqueous phase-separated droplets via liposome stabilisation

  Bio-mimetic motion has been hard to achieve due to a lack of biocompatible conditions. Here, the authors report the creation of a liposome-stabilised aqueous PEG/dextran Pickering-like emulsion system with motion induced by the Marangoni effect and characterised by negative chemotaxis.

  • Shaobin Zhang
  • , Claudia Contini
  •  & Oscar Ces

• Article
  08 September 2020 | Open Access

  Long-term autophagy is sustained by activation of CCTβ3 on lipid droplets

  The source of phospholipids to generate autophagosomal membranes, particularly after prolonged starvation, is not well characterized. Here, the authors show that CCTβ3, the rate limiting enzyme in phosphatidylcholine synthesis, is activated on lipid droplets and sustains long-term autophagy.

  • Yuta Ogasawara
  • , Jinglei Cheng
  •  & Toyoshi Fujimoto

• Article
  11 October 2019 | Open Access

  A Chlamydia pneumoniae adhesin induces phosphatidylserine exposure on host cells

  The Chlamydia pneumoniae adhesin LIPP plays a role in host cell entry and infection. Here, the authors find that LIPP binds to the host plasma membrane and mediates phosphatidylserine translocation, enhancing pathogen internalization without induction of apoptosis.

  • Jan N. Galle
  • , Tim Fechtner
  •  & Johannes H. Hegemann

• Article
  02 September 2019 | Open Access

  An electrostatic switching mechanism to control the lipid transfer activity of Osh6p

  Osh6p and Osh7p are yeast lipid transfer proteins (LTPs) that must transiently interact with membranes but how they escape from the electrostatic attraction of the plasma membrane is unclear. Here authors show that Osh6p reduces its avidity for anionic membranes once it captures PS or PI4P, due to a molecular lid closing its lipid-binding pocket.

  • Nicolas-Frédéric Lipp
  • , Romain Gautier
  •  & Guillaume Drin

• Article
  04 April 2019 | Open Access

  Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities

  Phox homology (PX) domains are membrane interacting domains that bind to various lipids. Here authors screen all human PX domains systematically for their phospholipid preferences and define four classes and provide the basis for defining and predicting functional PX-membrane interactions.

  • Mintu Chandra
  • , Yanni K.-Y. Chin
  •  & Brett M. Collins

• Article
  29 March 2019 | Open Access

  Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc₁ complex function

  Phosphatidylethanolamine (PE) is synthesized by four separate pathways, although surprisingly, perturbing mitochondrial PE synthesis compromises mitochondrial function. Here, the authors show that mitochondrial PE synthesis is required for Complex III function and challenge PE trafficking dogma.

  • Elizabeth Calzada
  • , Erica Avery
  •  & Steven M. Claypool

• Article
  17 January 2019 | Open Access

  A minimal biochemical route towards de novo formation of synthetic phospholipid membranes

  The origin of phospholipids, the primary constituents of cell membranes, is uncertain. Here, the authors develop an in vitro system to synthesize phospholipid molecules from water-soluble single-chain amphiphilic precursors via a reaction catalysed by the mycobacterial ligase FadD10.

  • Ahanjit Bhattacharya
  • , Roberto J. Brea
  •  & Neal K. Devaraj

• Article
  04 December 2018 | Open Access

  Neurohormonal signaling via a sulfotransferase antagonizes insulin-like signaling to regulate a Caenorhabditis elegans stress response

  Reduced insulin-like signaling is required for C. elegans response to many environmental stressors, but how distinct outcomes are achieved is unknown. The authors show that the cytosolic sulfotransferase SSU-1 controls neurohormonal signaling via NHR-1 to specify the animals’ osmotic stress response.

  • Nicholas O. Burton
  • , Vivek K. Dwivedi
  •  & H. Robert Horvitz

• Article
  14 August 2018 | Open Access

  Gating mechanism of the extracellular entry to the lipid pathway in a TMEM16 scramblase

  Some TMEM16 family members are Ca²⁺-dependent phospholipid scramblases, which also mediate non-selective ion transport; however, the mechanism how lipids permeate through the TMEM16 remains poorly understood. Here, the authors combine biochemical assays and simulations to identify the key steps regulating lipid movement through the membrane-exposed groove.

  • Byoung-Cheol Lee
  • , George Khelashvili
  •  & Alessio Accardi

• Article
  27 June 2018 | Open Access

  Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy

  Melanoma patients harbouring BRAF^V600E mutation generally develop resistance to targeted therapy. In this study, the authors demonstrate that SREBP-1-mediated induction of lipid biosynthesis contributes to therapy resistance in BRAF mutant melanoma.

  • Ali Talebi
  • , Jonas Dehairs
  •  & Johannes V. Swinnen

• Article
  12 June 2018 | Open Access

  Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells

  During atherosclerosis, endothelial cells release purines in response to oxidized phospholipids. Here, Hitzel et al. show that oxidized phospholipids activate an MTHFD2-regulated gene network in endothelial cells which reprograms amino acid metabolism towards production of purines and thus compensates for their loss.

  • Juliane Hitzel
  • , Eunjee Lee
  •  & Ralf P. Brandes

• Article
  24 May 2018 | Open Access

  Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation

  Myotube formation by fusion of myoblasts is essential for skeletal muscle formation, but which molecules regulate this process remains elusive. Here authors identify the mechanosensitive PIEZO1 channel as a key element, whose activity is regulated by phosphatidylserine during myotube formation.

  • Masaki Tsuchiya
  • , Yuji Hara
  •  & Masato Umeda

• Article
  22 November 2017 | Open Access

  Structural insights into the committed step of bacterial phospholipid biosynthesis

  The first step in bacterial phospholipid biosynthesis is the acylation of glycerol 3-phosphate to form lysophosphatidic acid. Here, the authors present the high resolution crystal structure of the glycerol 3-phosphate acyltransferase PlsY, a membrane protein and give insights into its catalytical mechanism.

  • Zhenjian Li
  • , Yannan Tang
  •  & Dianfan Li

• Article
  23 June 2016 | Open Access

  Arf6 controls retromer traffic and intracellular cholesterol distribution via a phosphoinositide-based mechanism

  The small GTPase Arf6 regulates intracellular transport, phosphoinositide signalling and cholesterol homeostasis. Here, Marquer et al. show that loss of Arf6 causes cholesterol accumulation in endosomes due to defects in phosphoinositide-dependent retromer-mediated trafficking of CI-M6PR and NPC2.

  • Catherine Marquer
  • , Huasong Tian
  •  & Gilbert Di Paolo

• Article
  01 February 2016 | Open Access

  Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding

  Export of Plasmodium falciparum proteins into infected erythrocytes relies upon the PEXEL motif in target proteins. Here Boddey et al.challenge the hypothesis that the PEXEL motif mediates export by binding PI(3)P and instead suggest it acts via cleavage by plasmepsin V.

  • Justin A. Boddey
  • , Matthew T. O’Neill
  •  & Alan F. Cowman

• Article
  06 October 2015 | Open Access

  Acidic phospholipids govern the enhanced activation of IgG-B cell receptor

  Adaptive immunity is the memory of previously experienced pathogens, where B cells establish a rapid antibody response upon IgG-B cell receptor activation. Here, Chen et al. show that sequestration of the cytoplasmic domain of mIgG by plasma membrane phospholipids prevents inappropriate activation of IgG-BCR signalling.

  • Xiangjun Chen
  • , Weiling Pan
  •  & Wanli Liu

• Article | 27 July 2015

  A phospholipid uptake system in the model plant Arabidopsis thaliana

  P4-type ATPases flip lipids from one side of a membrane to the other. Here Poulsen et al. show that ALA10, a P4 ATPase from Arabidopsis thaliana, internalizes phospholipids from the outside of plant cells and suggest that this uptake may be physiologically important for lipid signalling events.

  • Lisbeth R. Poulsen
  • , Rosa L. López-Marqués
  •  & Michael Palmgren

• Article
  10 March 2015 | Open Access

  Supramolecular synergy in the boundary lubrication of synovial joints

  Interacting cartilage surfaces in synovial joints experience very low levels of friction, allowing unhindered mechanical motion. Here, the authors propose how a synergistic interaction of hyaluronan, lubricin and phospholipids, molecules that are ubiquitous in joints, may lead to this high level of lubrication.

  • Jasmine Seror
  • , Linyi Zhu
  •  & Jacob Klein

• Article | 04 October 2011

  Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

  The role of phosphatidylinositol(4,5)bisphosphate in exocytosis is unclear. This study shows that inhibition of the p110δ isoform of PI3-kinase promotes a transient increase in phosphatidylinositol(4,5)bisphosphate, leading to a potentiation of exocytosis in chromaffin cells.

  • Peter J. Wen
  • , Shona L. Osborne
  •  & Frédéric A. Meunier