Membrane trafficking

  • Article
    | Open Access

    Molecular tethers physically bridge transport vesicles to their target membranes as a prerequisite step for fusion. Here the authors control vesicle tethering using optogenetic approaches to study the interplay between vesicle tethering and fusion.

    • Seong J. An
    • , Felix Rivera-Molina
    •  & Derek Toomre
  • Article
    | Open Access

    Transport protein particle (TRAPP) is a multimeric protein complex regulating membrane trafficking pathways. Here the authors show that TRAPPC4, a core subunit of TRAPP complex, is required for RAB11-mediated recycling of PD-L1, affecting T-cell-mediated anti-tumor immune responses.

    • Yimeng Ren
    • , Yun Qian
    •  & Jing-Yuan Fang
  • Article
    | Open Access

    Dynamin mediates the fission of vesicles during endocytosis. Here, the authors report the cryoEM structure of a super-constricted two-start dynamin 1 filament- one of the two known helical forms of dynamin, with insights into the molecular mechanisms of dynamin-mediated membrane scission.

    • Jiwei Liu
    • , Frances Joan D. Alvarez
    •  & Peijun Zhang
  • Article
    | Open Access

    The Spike protein of SARS-CoV-2 has a C-terminal cytoplasmic tail. Here the authors show that this tail binds trafficking machinery via sequences that appear optimised to ensure that Spike accumulates at the site of viral budding in the Golgi but that some can also traffic to the cell surface to induce syncytia formation.

    • Jérôme Cattin-Ortolá
    • , Lawrence G. Welch
    •  & Sean Munro
  • Article
    | Open Access

    Cells locally expand and retract their surface in response to environmental factors such as changes in membrane tension. Here the authors show the membrane adapter, dynamin2, locally constricts surface membrane to form an isolated but contiguous membrane reservoir that can open upon phospholipid scrambling via TMEM16F.

    • Christine Deisl
    • , Donald W. Hilgemann
    •  & Michael Fine
  • Article
    | Open Access

    Salmonella secretes the effector protein SopD into the host cell cytoplasm, leading to scission of the plasma membrane through unclear mechanisms. Here, Boddy et al. show that SopD binds to and inhibits the small GTPase Rab10, thus promoting removal of Rab10 and recruitment of dynamin-2 to drive plasma membrane scission.

    • Kirsten C. Boddy
    • , Hongxian Zhu
    •  & John H. Brumell
  • Article
    | Open Access

    Epithelial cells that organise into structures that contain a lumen are polarised. Here, the authors show that the short intracellular domain of transmembrane protein CD13 is required to capture endosomes at the apical site and is required for the polarisation of cells.

    • Li-Ting Wang
    • , Abira Rajah
    •  & Luke McCaffrey
  • Article
    | Open Access

    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
    | Open Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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