Article
|
Open Access
Featured
-
-
Article
| Open AccessExtracellular vesicles and exosomes generated from cystic renal epithelial cells promote cyst growth in autosomal dominant polycystic kidney disease
Autosomal dominant polycystic kidney disease is characterized by the formation of cysts in the kidney. Here the authors show that cystic extracellular vesicles/exosomes play a critical role in regulating the biology and function of adjacent cells, including renal epithelial cells, fibroblasts and macrophages, and contribute to renal cyst growth.
- Hao Ding
- , Linda Xiaoyan Li
- & Xiaogang Li
-
Article
| Open AccessYAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion
Cells in many tissues fuse into syncytia acquiring new functions. By investigating whether physical remodelling promotes differentiation, here, the authors show that plasma membrane diminution post-fusion causes transient nutrient stress that inhibits YAP1 activity and may reduce proliferation-promoting transcription.
- Daniel Feliciano
- , Carolyn M. Ott
- & Jennifer Lippincott-Schwartz
-
Article
| Open AccessSpecificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9
Extracellular vesicles (EVs) play a role in intercellular communication, however the precise biogenesis of different populations of EVs are not clear. Here, the authors follow the intracellular trafficking of two proteins before their secretion in EVs and report the biogenesis and protein markers of EV subtypes: ectosomes budding from the plasma membrane as well as exosomes from late endosomes.
- Mathilde Mathieu
- , Nathalie Névo
- & Clotilde Théry
-
Article
| Open AccessSphingolipids mediate polar sorting of PIN2 through phosphoinositide consumption at the trans-Golgi network
Lipid composition impacts the function of cellular membranes. Here the authors show that a reduction in sphingolipid acyl-chain length promotes phosphoinositide consumption by phospholipase C at the Arabidopsis trans-Golgi network which in turn regulates sorting of the auxin efflux carrier PIN2.
- Yoko Ito
- , Nicolas Esnay
- & Yohann Boutté
-
Article
| Open AccessThe nanoscale molecular morphology of docked exocytic dense-core vesicles in neuroendocrine cells
The molecular organization of exocytic vesicles regulates their transport and fusion. Prasai, Taraska, and colleagues use correlative light and electron microscopy, along with 3D tomography and gold labeling, to directly map proteins on single exocytic organelles at the plasma membrane.
- Bijeta Prasai
- , Gideon J. Haber
- & Justin W. Taraska
-
Article
| Open AccessIntracellular localisation of Mycobacterium tuberculosis affects efficacy of the antibiotic pyrazinamide
Effective chemotherapies against tuberculosis must kill the pathogen’s intracellular population. Here, Santucci et al. show that bacterial localisation within human macrophages impact pyrazinamide (PZA) accumulation and efficacy, and that combination with a second antibiotic (bedaquiline) enhances PZA accumulation via a host-dependent process.
- Pierre Santucci
- , Daniel J. Greenwood
- & Maximiliano G. Gutierrez
-
Article
| Open AccessNanoscale 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
| Open AccessINPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer
The PI(3,4)P2 4-phosphatase, INPP4B, functions as a tumour suppressor in triple negative breast cancer. Here, the authors show that INPP4B enhances proliferation and growth of PIK3CA-mutant ER+ breast cancers by promoting PI3Kα-dependent late endosome formation and trafficking that leads to the activation of Wnt/β-catenin signalling.
- Samuel J. Rodgers
- , Lisa M. Ooms
- & Christina A. Mitchell
-
Article
| Open AccessDistinct EH domains of the endocytic TPLATE complex confer lipid and protein binding
AtEH/Pan1 proteins contain two N-terminal Eps15 homology (EH) domains and are subunits of the endocytic TPLATE complex present in plants. Here, the authors combine X-ray crystallography, NMR and MD simulations with biochemical and in planta analysis to characterize the two AtEH1/Pan1 EH domains and reveal their structural differences and complementary functional roles.
- Klaas Yperman
- , Anna C. Papageorgiou
- & Daniel Van Damme
-
Article
| Open AccessInositol triphosphate-triggered calcium release blocks lipid exchange at endoplasmic reticulum-Golgi contact sites
The interplay between non-vesicular lipid transport, calcium signaling, and membrane dynamics is unclear. Here, the authors report a function for inositol triphosphate hydrolysis by the inositol 5-phosphatase INPP5A in controlling lipid exchange at interorganelle membrane contact sites between the endoplasmic reticulum and Golgi.
- Mouhannad Malek
- , Anna M. Wawrzyniak
- & Volker Haucke
-
Article
| Open AccessCdk5 and GSK3β inhibit fast endophilin-mediated endocytosis
Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Here, the authors show that Cdk5 and GSK3β are negative regulators of fast Endophilin-mediated endocytosis (FEME).
- Antonio P. A. Ferreira
- , Alessandra Casamento
- & Emmanuel Boucrot
-
Article
| Open AccessStructure of the complete, membrane-assembled COPII coat reveals a complex interaction network
Cytosolic coat proteins capture secretory cargo and sculpt membrane carriers for intracellular transport, such as COPII which mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Here authors visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers.
- Joshua Hutchings
- , Viktoriya G. Stancheva
- & Giulia Zanetti
-
Article
| Open AccessSelective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs
Mitochondrial content in extracellular vesicles (EVs) can enhance inflammation, although its role in noninflammatory conditions is unclear. Here, the authors show that mitochondria-derived vesicles target material to EVs, whereas Parkin directs damaged mitochondrial content to lysosomes, providing insight into mitochondria-driven immune responses.
- Kiran Todkar
- , Lilia Chikhi
- & Marc Germain
-
Article
| Open AccessCargo sorting zones in the trans-Golgi network visualized by super-resolution confocal live imaging microscopy in plants
The trans-Golgi network (TGN) serves as a platform to sort and transport proteins to their final destinations. Here the authors show that the TGN of Arabidopsis consists of spatially and temporally distinct subregions and propose that these zones may sort cargo to different destinations.
- Yutaro Shimizu
- , Junpei Takagi
- & Akihiko Nakano
-
Article
| Open AccessQuantitative characterization of extracellular vesicle uptake and content delivery within mammalian cells
Extracellular vesicles mediate cell–cell communication, however, their capacity to deliver their content within acceptor cells is unclear. Here, the authors develop a quantitative assay and show that release of extracellular vesicle contents requires endosomal acidification and may involve membrane fusion.
- Emeline Bonsergent
- , Eleonora Grisard
- & Grégory Lavieu
-
Article
| Open AccessMissense mutation of Fmr1 results in impaired AMPAR-mediated plasticity and socio-cognitive deficits in mice
The R138Q mutation in the Fragile X Mental Retardation 1 (FMR1) gene has been associated with Fragile X syndrome (FXS). Here, the authors present a Fmr1R138Q Knock-In mouse model and show that R138Q mutation results in impaired long-term potentiation and socio-cognitive performance in these mice.
- Marta Prieto
- , Alessandra Folci
- & Stéphane Martin
-
Article
| Open AccessOxidation inhibits autophagy protein deconjugation from phagosomes to sustain MHC class II restricted antigen presentation
LC3-associated phagocytosis (LAP) is a non-canonical use of the autophagy machinery that can contribute to immune responses. Here, the authors describe the mechanism by which ROS production regulates LAPosome stabilization sustaining MHC II dependent antigen presentation.
- Laure-Anne Ligeon
- , Maria Pena-Francesch
- & Christian Münz
-
Article
| Open AccessDrebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking
Reactive astrocytes control tissue damage following traumatic brain injury. Here the authors show that Drebrin (DBN) regulates scar formation and astrocyte reactivity in mice. Astrocytic DBN plays its neuroprotective role through the mediation of membrane trafficking.
- Juliane Schiweck
- , Kai Murk
- & Britta J. Eickholt
-
Article
| Open AccesspHmScarlet is a pH-sensitive red fluorescent protein to monitor exocytosis docking and fusion steps
A number of pH-sensitive fluorescent proteins exist which enable monitoring of some but not all steps of exocytosis. Here the authors engineer a bright, photostable red pH-sensitive fluorescent protein, pHmScarlet, to allow visualisation of the docking and fusion events of exocytosis.
- Anyuan Liu
- , Xiaoshuai Huang
- & Pingyong Xu
-
Article
| Open AccessAn ESCRT-dependent step in fatty acid transfer from lipid droplets to mitochondria through VPS13D−TSG101 interactions
Metabolic rewiring requires the mobilization of fatty acids (FA) from lipid droplets (LDs) at membrane contact sites (MCSs), although the details of FA transfer remain unclear. Here, the authors show that VPS13D and the ESCRT complex remodel LD membranes to promote FA trafficking to mitochondria.
- Jingru Wang
- , Na Fang
- & Wei-Ke Ji
-
Article
| Open AccessCavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
Caveolae are spherical nanodomains of the plasma membrane generated by assembly of caveolin and cavin proteins. Here, the authors show that fuzzy electrostatic interactions between caveolin-1 and Cavin1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.
- Vikas A. Tillu
- , James Rae
- & Brett M. Collins
-
Article
| Open AccessAsynchronous release sites align with NMDA receptors in mouse hippocampal synapses
Action potentials induce synchronous and asynchronous release of neurotransmitters. Here, the authors show that the synchronous and asynchronous release sites are aligned with AMPARs and NMDARs, respectively, in mouse hippocampal synapses. This organization allows efficient activation of NMDARs.
- Shuo Li
- , Sumana Raychaudhuri
- & Shigeki Watanabe
-
Article
| Open AccessHomeostatic regulation of STING by retrograde membrane traffic to the ER
COPA regulates Golgi to ER transport, and mutations lead to autoinflammation and disease through poorly understood mechanisms. Here, the authors show that disease-causing COPA variants prevent STING transport from the Golgi to the ER, leading to cGAS-independent activation of the STING pathway.
- Kojiro Mukai
- , Emari Ogawa
- & Tomohiko Taguchi
-
Article
| Open AccessSmall molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells
The tumour microenvironment provides signals to support leukaemic stem cells (LSC) maintenance and chemoresistance. Here, the authors show that disrupting niche-associated signalling by inhibiting receptor-mediated endocytosis with a dynamin GTPase inhibitor overcomes chemoresistance of LSC.
- Cedric S. Tremblay
- , Sung Kai Chiu
- & David J. Curtis
-
Article
| Open AccessA trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export
Lysosomes play an important role in cellular LDL-cholesterol uptake. Here, the authors perform a genome-wide genetic screen for cholesterol regulators and identify C18orf8 as a conserved subunit of a trimeric Rab7 GEF that controls LDL trafficking and NPC1-dependent lysosomal cholesterol export.
- Dick J. H. van den Boomen
- , Agata Sienkiewicz
- & Paul J. Lehner
-
Article
| Open AccessCrbn modulates calcium influx by regulating Orai1 during efferocytosis
Calcium flux must be carefully controlled during the phagocytosis of apoptotic cells (efferocytosis), although how this occurs is not fully understood. Here, the authors show that the Cereblon E3 ligase regulates Orai1 degradation and subsequently SOCE-mediated calcium influx.
- Hyunji Moon
- , Chanhyuk Min
- & Daeho Park
-
Article
| Open AccessMechanism and evolution of the Zn-fingernail required for interaction of VARP with VPS29
VARP is bound to endosomes and functions as a protein:protein interaction platform. Here, the authors present the NMR structure of the complex between the retromer subunit VPS29 and a VARP Zn-fingernail microdomain that is structurally distinct from Zn-fingers and further show that mutations, which abolish VPS29:VARP binding, inhibit trafficking from endosomes to the cell surface.
- Harriet Crawley-Snowdon
- , Ji-Chun Yang
- & David J. Owen
-
Article
| Open AccessCD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis
The mechanistic details of fatty acid uptake into cells remains poorly understood. Here, the authors identify CD36 internalization via cavaeolae and demonstrate dynamic palmitoylationof CD36 is required for endocytic uptake of fatty acids.
- Jian-Wei Hao
- , Juan Wang
- & Tong-Jin Zhao
-
Article
| Open AccessA molecular sensor to quantify the localization of proteins, DNA and nanoparticles in cells
Determining the trafficking of intracellular material is commonly done by colocalisation analysis using microscopy. Here the authors monitor trafficking of select cargo by measuring the conversion of quenched SNAP-tag substrates by subcellularly-localised SNAP-tag and detection by flow cytometry.
- Laura I. FitzGerald
- , Luigi Aurelio
- & Angus P. R. Johnston
-
Article
| Open AccessChlorpromazine eliminates acute myeloid leukemia cells by perturbing subcellular localization of FLT3-ITD and KIT-D816V
Receptor tyrosine kinase mutations are frequent and associated with poor prognosis in acute myeloid leukemia (AML). Here the authors show that the antipsychotic drug chlorpromazine reduces AML cells viability by perturbing the intracellular localization of FLT3-ITD and KIT-D816V.
- Shinya Rai
- , Hirokazu Tanaka
- & Itaru Matsumura
-
Article
| Open AccessEpsin-mediated degradation of IP3R1 fuels atherosclerosis
Endothelial cell (EC) dysfunction and inflammation contribute to plaque destabilization in atherosclerosis, increasing the risk of thrombotic events. Here, the authors show that epsin promotes EC inflammation via a mechanism involving IP3R1 degradation, and that deletion of epsin in the endothelium prevents EC dysfunctoin and atherosclerosis in mice.
- Yunzhou Dong
- , Yang Lee
- & Hong Chen
-
Article
| Open AccessMutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
p53 mutants can promote tumorigenesis by affecting fundamental cellular pathways and functions. In this study, the authors demonstrate a novel mutant-p53/HIF1α/miR-30d axis that impacts Golgi structure, trafficking, and secretion of proteins essential for tumor growth and metastasis.
- Valeria Capaci
- , Lorenzo Bascetta
- & Giannino Del Sal
-
Article
| Open AccessContacting domains segregate a lipid transporter from a solute transporter in the malarial host–parasite interface
While membrane contact sites between intracellular organelles are abundant, little is known about the contacts between membranes that delimit extracellular junctions within cells, such as intracellular parasites. Here authors demonstrate the segregation of a lipid transporter from a solute transporter in the malarial host-parasite interface.
- Matthias Garten
- , Josh R. Beck
- & Joshua Zimmerberg
-
Article
| Open AccessPDZD8 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
| Open AccessA self-sustaining endocytic-based loop promotes breast cancer plasticity leading to aggressiveness and pro-metastatic behavior
It is unclear if genetic alterations in endocytic proteins play a causal role in high incidence human cancers. Here, the authors report the oncogenic role of Epsin3 (EPN3) in breast cancer, and show EPN3 to drive tumorigenesis through induction of a partial epithelial mesenchymal transition state and a TGFβ-dependent regulatory loop that promotes cellular plasticity and invasive behaviour.
- Irene Schiano Lomoriello
- , Giovanni Giangreco
- & Pier Paolo Di Fiore
-
Article
| Open AccessTECPR1 promotes aggrephagy by direct recruitment of LC3C autophagosomes to lysosomes
Many neurodegenerative disorders are characterised by the accumulation of protein aggregates in neurons. Here, the authors show that the lysosomal protein TECPR1 selectively recruits mature autophagosomes via an interaction with LC3C to break down protein aggregates in neural stem cells.
- Lisa Wetzel
- , Stéphane Blanchard
- & Thomas Wollert
-
Article
| Open AccessAutophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling
NMDA receptor-dependent long-term depression (NMDAR-LTD) is a form of synaptic plasticity mediated by reduced recycling of AMPA receptors to the plasma membrane. Here the authors show that autophagy is a regulator of this endocytic recycling and autophagy upregulation dampens NMDAR-LTD in adulthood.
- Hongmei Shen
- , Huiwen Zhu
- & Zheng Li
-
Article
| Open AccessRab35-regulated lipid turnover by myotubularins represses mTORC1 activity and controls myelin growth
Charcot-Marie-Tooth (CMT) is an inherited peripheral neuropathy. Here, the authors show that Rab35 forms a complex with genes implicated in CMT, MTMR13 and MTMR2, which regulates myelin growth by controlling mTORC1 signaling through lipid turnover.
- Linda Sawade
- , Federica Grandi
- & Volker Haucke
-
Article
| Open AccessHuman ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation
ESCRT-III complexes assemble in vivo inside membrane structures with a negative Gaussian curvature, but how membrane shape influences ESCRT-III polymerization remains unclear. Here authors use structural and biophysical methods to show how human ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation.
- Aurélie Bertin
- , Nicola de Franceschi
- & Patricia Bassereau
-
Article
| Open AccessVesicular transport mediates the uptake of cytoplasmic proteins into mitochondria in Drosophila melanogaster
Mitochondrial dynamics change during ageing, with larger mitochondria and altered protein import in older animals. Here the authors show that Dosmit protein mediates mitochondrial morphology with Rab32 by inducing double-membraned vesicles that regulate protein trafficking into mitochondria.
- Po-Lin Chen
- , Kai-Ting Huang
- & Chun-Hong Chen
-
Article
| Open AccessA live cell reporter of exosome secretion and uptake reveals pathfinding behavior of migrating cells
A prior live-cell exosome reporter showed dim fluorescence and could not be expressed stably, limiting its usefulness. Here the authors stabilise the reporter to allow long-term tracking of exosomes, and incorporate a second fluorophore to visualise the entire exosome lifecycle.
- Bong Hwan Sung
- , Ariana von Lersner
- & Alissa M. Weaver
-
Article
| Open AccessParacrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes
Glucagon is elevated Type-2 diabetes, which contributes to poor glucose control in patients with the disease. Here the authors report that secretion of the hormone is controlled by paracrine inhibition, and that resistance of α-cells to somatostatin can explain hyperglucagonemia in type-2 diabetes.
- Muhmmad Omar-Hmeadi
- , Per-Eric Lund
- & Sebastian Barg
-
Article
| Open AccessKinesin-1 regulates antigen cross-presentation through the scission of tubulations from early endosomes in dendritic cells
Kinesin-1 is a motor protein transporting cargo along microtubules. Here the authors show that kinesin-1 is required for antigen cross-presentation and coordinates endosome scission from early endosomes to allow sorting internalized cargoes towards the recycling endosomal or lysosomal compartments.
- Meriem Belabed
- , François-Xavier Mauvais
- & Gaël Ménasché
-
Article
| Open AccessPan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway
Imidazolopiperazines (IZPs) are a class of compounds under clinical development for malaria, but their mechanism of action is unclear. Here, the authors show that IZPs inhibit the parasite’s secretory pathway, affecting protein trafficking and export.
- Gregory M. LaMonte
- , Frances Rocamora
- & Elizabeth A. Winzeler
-
Article
| Open AccessThe cryo-EM structure of the SNX–BAR Mvp1 tetramer
SNX-BAR proteins are a family of PX and BAR domain-containing proteins with pivotal roles in trafficking processes. Here authors present the cryo-EM structure of the full-length fungal SNX-BAR Mvp1, which is an autoinhibited tetramer and provides critical insight into SNX-BAR function and regulation.
- Dapeng Sun
- , Natalia V. Varlakhanova
- & Marijn G. J. Ford
-
Article
| Open AccessEndophilin-A3 and Galectin-8 control the clathrin-independent endocytosis of CD166
How and which cell surface molecules are taken up by clathrin-independent endocytosis is an ongoing area of research. Here, the authors show that the tumor marker CD166 is a clathrin-independent cargo that is taken up by endophilin-A3 and galectin-8, which regulates cancer cell migration.
- Henri-François Renard
- , François Tyckaert
- & Pierre Morsomme
-
Article
| Open AccessAcid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
Macrophages are critical in limiting replication of herpes simplex virus type 1 (HSV-1). Here the authors show how acid ceramidase and its enzymatic product sphingosine enable multivesicular bodies to function as an anti-viral mechanism.
- Judith Lang
- , Patrick Bohn
- & Karl S. Lang
-
Article
| Open AccessPharmacological induction of selective endoplasmic reticulum retention as a strategy for cancer therapy
Inhibition of PERK, an endoplasmic reticulum (ER) unfolded protein response (UPR) protein, is a potential pharmacological target for cancer treatment. Here, the authors show that inhibition of PERK under ER stress affects trafficking from the ER to the surface of several key receptor tyrosine kinases, suggesting a selective ER retention.
- Mohamed Mahameed
- , Shatha Boukeileh
- & Boaz Tirosh
-
Article
| Open AccessEndophilin-A coordinates priming and fusion of neurosecretory vesicles via intersectin
Endophilins-A are conserved membrane-associated proteins required for endocytosis. Here, the authors report that endophilins-A also promote exocytosis of neurosecretory vesicles by coordinating priming and fusion through intersectin-1, independently of their roles in different types of endocytosis.
- Sindhuja Gowrisankaran
- , Sébastien Houy
- & Ira Milosevic