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| Open AccessThe intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation
Cell surface receptors are thought to be internalized via the multivesicular bodies (MVBs) in an ESCRT-dependent pathway. Here, the authors report that in yeast, a hexose transporter is internalized via an ESCRT-independent pathway into intralumenal fragments (ILF).
- Erin Kate McNally
- & Christopher Leonard Brett
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Article
| Open AccessMechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells
Plasma membrane tension is an important factor that regulates many key cellular processes. Here authors show that a specific dynamin-independent endocytic pathway is modulated by changes in tension via the mechano-transducer vinculin.
- Joseph Jose Thottacherry
- , Anita Joanna Kosmalska
- & Satyajit Mayor
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Article
| Open AccessSynergy between intrinsically disordered domains and structured proteins amplifies membrane curvature sensing
Many proteins which sense membrane curvature contain intrinsically disordered domains. Here the authors use Monte Carlo simulations combined with experimental approaches and report that disordered domains are potent sensors of membrane curvature.
- Wade F. Zeno
- , Upayan Baul
- & Jeanne C. Stachowiak
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Article
| Open AccessFerriTag is a new genetically-encoded inducible tag for correlative light-electron microscopy
Correlative light-electron microscopy (CLEM) pairs versatile fluorescence imaging with high resolution electron microscopy. Here, the authors develop a genetically-encoded, chemically-inducible tag that allows acute labeling of single proteins for CLEM.
- Nicholas I. Clarke
- & Stephen J. Royle
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Article
| Open AccessSmall GTPases and BAR domain proteins regulate branched actin polymerisation for clathrin and dynamin-independent endocytosis
Several endocytic pathways operate simultaneously at the cell surface, including the clathrin and dynamin-independent CLIC/GEEC (CG) pathway. Here the authors show that small GTPases and BAR domain proteins regulate branched actin to make clathrin and dynamin-independent endocytic vesicles.
- Mugdha Sathe
- , Gayatri Muthukrishnan
- & Satyajit Mayor
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Article
| Open AccessClathrin-adaptor ratio and membrane tension regulate the flat-to-curved transition of the clathrin coat during endocytosis
The sequence of structural and molecular events during clathrin-mediated endocytosis is unclear. Here the authors combine correlative microscopy and simple mathematical growth laws to demonstrate that the flat patch starts to curve when around 70% of the final clathrin content is reached.
- Delia Bucher
- , Felix Frey
- & Steeve Boulant
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Article
| Open AccessMembrane bending occurs at all stages of clathrin-coat assembly and defines endocytic dynamics
Two distinct and opposing models for clathrin-mediated endocytosis have been inferred from EM and structural biology data. Here the authors develop an optical method to directly visualize membrane-bending dynamics and show that coat assembly accommodates membrane bending during or after the assembly of the clathrin lattice, which is not predicted by either model.
- Brandon L. Scott
- , Kem A. Sochacki
- & Adam D. Hoppe
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Article
| Open AccessEpsin and Sla2 form assemblies through phospholipid interfaces
Adapter proteins assist clathrin coated pit assembly. Here, the authors combine native mass spectrometry, crystallography and SAXS measurements and show that the membrane–proximal domains of the adaptor proteins epsin and Sla2 form complexes mediated through phosphatidylinositol 4,5-bisphosphate interfaces leading to assembly formation.
- Maria M. Garcia-Alai
- , Johannes Heidemann
- & Rob Meijers
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Article
| Open AccessEndocytosis regulates TDP-43 toxicity and turnover
Impaired turnover of TDP-43 by impaired autophagy or proteasomal function have been suggested to be the cause of TDP-43 accumulation, a hallmark of ALS. Here the authors demonstrate that endocytosis is also important for regulating TDP-43 turnover and toxicity.
- Guangbo Liu
- , Alyssa N. Coyne
- & J. Ross Buchan
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Article
| Open AccessMagnesium uptake by connecting fluid-phase endocytosis to an intracellular inorganic cation filter
Metal bioavailability is frequently limited by sequestering agents which makes them inaccessible to cells. Here the authors show that cells can increase Mg2+ uptake via fluid phase endocytosis and accumulate this metal in their vacuole loaded with polyphosphate, and later can be exported to the cytosol.
- Sandra H. Klompmaker
- , Kid Kohl
- & Andreas Mayer
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Article
| Open AccessLow pH-induced conformational change and dimerization of sortilin triggers endocytosed ligand release
Sortilin is an endocytosis receptor with a luminal β-propeller domain. Here the authors present the structures of the β-propeller domain at neutral and acidic pH, which reveal that sortilin dimerises and undergoes conformational changes at low pH and further propose a model for low pH-induced ligand release by endocytosis receptors.
- Nadia Leloup
- , Philip Lössl
- & Bert J. C. Janssen
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Article
| Open AccessPhospholipid flippase ATP11C is endocytosed and downregulated following Ca2+-mediated protein kinase C activation
ATP11C is a flippase that uses ATP hydrolysis to translocate phospholipids at the plasma membrane. Here, the authors show that the activation of Ca2+-dependent protein kinase C increases ATP11C endocytosis thus downregulating phospholipid translocation.
- Hiroyuki Takatsu
- , Masahiro Takayama
- & Hye-Won Shin
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Article
| Open AccessRSV glycoprotein and genomic RNA dynamics reveal filament assembly prior to the plasma membrane
Assembly of filamentous RSV particles is incompletely understood due to a lack of techniques suitable for live-cell imaging. Here Vanover et al. use labeled soybean agglutinin to selectively label RSV G protein and show how filamentous RSV assembly, initiated in the cytoplasm, uses G protein recycled from the plasma membrane.
- Daryll Vanover
- , Daisy V. Smith
- & Philip J. Santangelo
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Article
| Open AccessSRpHi ratiometric pH biosensors for super-resolution microscopy
Ratiometric fluorescent pH probes are useful tools to monitor acidification of vesicles during endocytosis, but the size of vesicles is below the diffraction limit. Here the authors develop a family of ratiometric pH sensors for use in STED super-resolution microscopy, and optimize their delivery to endosomes.
- Douglas S. Richardson
- , Carola Gregor
- & Stefan W. Hell
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Article
| Open AccessPlanar polarized Rab35 functions as an oscillatory ratchet during cell intercalation in the Drosophila epithelium
Various stages of tissue morphogenesis involve the contraction of epithelial surfaces. Here, the authors identify the Rab GTPase Rab35 as an essential component of this contractile process, which functions as a membrane ratchet to ensure unidirectional movement of intercalating cells.
- Cayla E. Jewett
- , Timothy E. Vanderleest
- & J. Todd Blankenship
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Article
| Open AccessAGC family kinase 1 participates in trogocytosis but not in phagocytosis in Entamoeba histolytica
Entamoeba histolytica can kill host cells by trogocytosis, while it ingests dead cells by phagocytosis. Here, Somlata et al. show that EhAGCK1, an AGC family kinase, is specifically involved in trogocytosis, shedding light on the molecular differences between trogocytosis and phagocytosis.
- Somlata
- , Kumiko Nakada-Tsukui
- & Tomoyoshi Nozaki
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Article
| Open AccessFlat clathrin lattices are dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling of specific receptors
Clathrin lattices coat flat membrane regions, called plaques, whose regulation and function are poorly understood. Here the authors find that plaques are regulated by actin dynamics and contain both the endocytic and the cell adhesion machineries, and are involved in endocytosis of specific cargos, and cell migration.
- Daniela Leyton-Puig
- , Tadamoto Isogai
- & Metello Innocenti
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| Open AccessLipid-mediated PX-BAR domain recruitment couples local membrane constriction to endocytic vesicle fission
The spatiotemporal regulation of membrane scaffolds recruitment and coupling between membrane deformation and fission in endocytosis are unclear. Here the authors show that lipid conversion at endocytic pits recruits SNX9, which couples local membrane constriction to fission in endocytosis.
- Johannes Schöneberg
- , Martin Lehmann
- & Frank Noé
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| Open AccessA new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling
Beta-arrestins play central roles in the mechanisms regulating GPCR signalling and trafficking. Here the authors identify a selective inhibitor of the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP-2, which they use to dissect the role of the β-arrestin/β2-adaptin interaction in GPCR signalling.
- Alexandre Beautrait
- , Justine S. Paradis
- & Michel Bouvier
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Article
| Open AccessFscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation
It is unclear how the cytoskeleton acts to assist in TGF-β signalling downstream of the receptor. Here, in zebrafish, the authors show that the actin-bundling protein FSCN1 interacts with TGF-β type I receptors ALK 4 and 5, enabling actin filament mediated vesicle trafficking and endoderm formation.
- Zhaoting Liu
- , Guozhu Ning
- & Qiang Wang
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Article
| Open AccessCholesterol and ORP1L-mediated ER contact sites control autophagosome transport and fusion with the endocytic pathway
Autophagy requires transport of autophagosomes to the perinuclear region. Here, the authors show that ORP1L localizes to autophagosomes and mediates formation of ER contact sites that prevent autophagosome transport and fusion with endocytic vesicles when cholesterol levels are low.
- Ruud H. Wijdeven
- , Hans Janssen
- & Jacques Neefjes
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Article
| Open AccessMitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification
Plant cells maintain strict proton gradients over different membranes. Here, Dejonghe et al. show that several protonophores, including the known tyrosine kinase inhibitor TyrphostinA23, inhibit clathrin-mediated endocytosis by disturbing these gradients and causing cytoplasmic acidification.
- Wim Dejonghe
- , Sabine Kuenen
- & Eugenia Russinova
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Article
| Open AccessHypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells
Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. Here, the authors show that caveolin-1 can down-regulate global membrane protein endocytosis in hypoxic cells with potential implications for targeting the hypoxic 3microenvironment of aggressive tumours.
- E. Bourseau-Guilmain
- , J. A. Menard
- & M. Belting
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Article
| Open AccessCalcium-sensing receptors signal constitutive macropinocytosis and facilitate the uptake of NOD2 ligands in macrophages
Macropinocytosis can be induced in several cell types by growth factors to promote nutrient acquisition. Here the authors find that constitutive macropinocytosis, unique to dendritic cells and macrophages, requires the activity of calcium-sensing receptors.
- Johnathan Canton
- , Daniel Schlam
- & Sergio Grinstein
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Article
| Open AccessPTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7
Rab7 is a critical GTPase for endosome maturation and it is implicated in the endocytic traffic of several receptors, including EGFR. In this study, the authors reveal the potential role of PTEN in the endocytic trafficking pathway of EGFR, which is dependent on its phosphatase activity through the direct post-translational modification of Rab7.
- Swapnil Rohidas Shinde
- & Subbareddy Maddika
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Article
| Open AccessIntegrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force
Force is known to recruit adaptor proteins to the intracellular tails of integrin extracellular matrix receptors. Here the authors show that matrix force-dependent β3 integrin signals block endocytosis by preventing the recruitment of the clathrin adaptor Dab2.
- Cheng-han Yu
- , Nisha Bte Mohd Rafiq
- & Michael P. Sheetz
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Article
| Open AccessStonin1 mediates endocytosis of the proteoglycan NG2 and regulates focal adhesion dynamics and cell motility
Signalling is often fine-tuned by the exo-endocytic cycling of cell surface receptors. Here, the authors show that the endocytic adaptor protein Stonin1 is important for the endocytosis of NG2, a co-receptor for extracellular matrix and growth factors, and that loss of Stonin1 alters cell motility.
- Fabian Feutlinske
- , Marietta Browarski
- & Tanja Maritzen
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Article
| Open AccessDiffusional spread and confinement of newly exocytosed synaptic vesicle proteins
Neurotransmission is mediated by synaptic vesicles (SVs) fusion with the plasma membrane near active zones. Here, Gimber et al.observe that rapid diffusional spread and confinement is followed by slow reclustering of SV proteins at the periactive endocytic zone through SV protein association with the clathrin-based machinery.
- Niclas Gimber
- , Georgi Tadeus
- & Volker Haucke
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Article
| Open AccessReal-time fluorescence imaging with 20 nm axial resolution
Mapping the nanoscale height and dynamics of structures within the cell is difficult. Here the authors present a two-wavelength total internal reflection fluorescence method to perform real-time imaging with nanometre axial resolution using a conventional microscope.
- Daniel R. Stabley
- , Thomas Oh
- & Khalid Salaita
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Article
| Open AccessActivity-regulated trafficking of the palmitoyl-acyl transferase DHHC5
Synaptic plasticity is mediated by the dynamic localization of proteins at synapses, which is partly controlled via palmitoylation of synaptic proteins. Here, the authors show how neuronal activity regulates the palmitoylation reaction through the translocation of the palmitoyl-acyl transferase DHHC5.
- G. Stefano Brigidi
- , Brendan Santyr
- & Shernaz X. Bamji
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Article
| Open AccessWASH and Tsg101/ALIX-dependent diversion of stress-internalized EGFR from the canonical endocytic pathway
Stress induces ligand-independent endocytosis of EGF receptor (EGFR), but its fate and role in signalling are not known. Here Tomas et al. show that stress-internalized EGFR accumulates and is retained in distinct multivesicular bodies, and delays the onset of stress-induced apoptosis.
- Alejandra Tomas
- , Simon O. Vaughan
- & Clare E. Futter
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| Open AccessDynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids
Recent data question the long-assumed link between caveolae and endocytosis of membrane proteins. Shvets et al. use genome editing to tag and trace endogenous caveolar proteins, providing evidence that these structures exclude membrane proteins and are instead required for proper sorting of excess membrane lipids.
- Elena Shvets
- , Vassilis Bitsikas
- & Benjamin J. Nichols
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CCM-3/STRIPAK promotes seamless tube extension through endocytic recycling
Mutations in the CCM3 gene in humans lead to severe forms of cerebral cavernous malformation. Here, Lant et al. shed light on the mechanism of CCM-3 function in C. elegans, and show that CCM-3 ablation leads to defects in excretory canal extension and the formation of cysts reminiscent of human malformations.
- Benjamin Lant
- , Bin Yu
- & W Brent Derry
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| Open AccessA balance between membrane elasticity and polymerization energy sets the shape of spherical clathrin coats
A relationship between membrane tension and clathrin polymerization during endocytosis has not been experimentally established. Here, the authors show using an in vitroreconstituted system and theoretical modelling that membrane tension regulates clathrin polymerization into spherical cages by varying the membrane budding energy.
- Mohammed Saleem
- , Sandrine Morlot
- & Aurélien Roux
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Membrane tension and peripheral protein density mediate membrane shape transitions
An ultrafast mechanism of endocytosis was recently discovered, and proposed to be dependent on local reduction in membrane tension. Shi and Baumgart provide experimental support for this hypothesis by quantifying the impact of membrane tension on membrane tubulation by endocytic proteins, such as endophilin A1.
- Zheng Shi
- & Tobias Baumgart
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An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability
CendR peptides, based on a C-terminal motif found in neuropilins, have been used to promote drug delivery to tumours by endocytosis. Pang et al. show that CendR peptides are taken up by a mechanistically distinct form of endocytosis that resembles macropinocytosis, and is stimulated by nutrient depletion.
- Hong-Bo Pang
- , Gary B. Braun
- & Erkki Ruoslahti
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Article
| Open AccessKainate receptor activation induces glycine receptor endocytosis through PKC deSUMOylation
Maintenance of proper membrane excitability is vital to neuronal function and in several neuronal types this relies on a balance between receptor-mediated excitation and inhibition. Here the authors report a crosstalk between excitatory kainate receptors and inhibitory glycine receptors that relies on the SUMOylation status of PKC.
- Hao Sun
- , Li Lu
- & Yong Li
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Article
| Open AccessLigand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1
G-protein coupled receptors can signal through G-proteins or through β-arrestin, however mechanisms determining pathway selection remain unclear. Here the authors show that the duration of cannabinoid receptor clustering in clathrin coated pits prior to endocytosis determines the strength of β-arrestin signalling.
- Jacqueline Flores-Otero
- , Kwang H. Ahn
- & Guillermo A. Yudowski
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Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole
Proteins from the trans-Golgi network and the plasma membrane are both targeted to the vacuole in a Rab5-dependent manner; however, it remains unclear where these two routes converge. Toshima et al.show that convergence occurs upstream of Rab5, and in doing so discover a Rab5-independent endocytic pathway.
- Junko Y. Toshima
- , Show Nishinoaki
- & Jiro Toshima
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Decreased CALM expression reduces Aβ42 to total Aβ ratio through clathrin-mediated endocytosis of γ-secretase
CALM is an adaptor protein required for clathrin-mediated endocytosis, and is a protective factor in Alzheimer’s disease. Here, Kanatsu et al.show that CALM can reduce the production of toxic Aß42 protein by driving clathrin-mediated endocytosis of γ-secretase.
- Kunihiko Kanatsu
- , Yuichi Morohashi
- & Takeshi Iwatsubo
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Post-fusion structural changes and their roles in exocytosis and endocytosis of dense-core vesicles
Fusion of vesicles with the plasma membrane generates omega-shaped intermediates that are thought to either dilate until flat or less frequently, undergo pore closure. Chiang et al.reveal that in chromaffin cells, these structures do not dilate, but change in size before pore closure or shrink until undetectable.
- Hsueh-Cheng Chiang
- , Wonchul Shin
- & Ling-Gang Wu
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Article |
A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection
Influenza virus can enter host cells through endocytosis, but the molecular pathways involved in this process are not fully understood. Here, the authors dissect these pathways and identify Ca2+as a key regulator of influenza A virus entry via both clathrin-mediated and clathrin-independent endocytosis.
- Yoichiro Fujioka
- , Masumi Tsuda
- & Yusuke Ohba
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Article
| Open AccessTubular endocytosis drives remodelling of the apical surface during epithelial morphogenesis in Drosophila
During epithelial morphogenesis in Drosophila, the villous apical cell surface is flattened. Fabrowski et al. show that this flattening depends on a dramatic increase in endocytosis associated with the formation of tubular invaginations, revealing a role for membrane trafficking in morphological remodelling.
- Piotr Fabrowski
- , Aleksandar S. Necakov
- & Stefano De Renzis
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Non-uniform membrane diffusion enables steady-state cell polarization via vesicular trafficking
The mechanism by which proteins become polarized to a specific cortical site in budding yeast cells has been a topic of recent debate. Slaughter et al.show that differing diffusion rates of Cdc42 within plasma membrane environments sustain the polarized state.
- Brian D. Slaughter
- , Jay R. Unruh
- & Rong Li
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Three-dimensional imaging of single nanotube molecule endocytosis on plasmonic substrates
Imaging and tracking the motion of single molecules on cell plasma membranes requires high spatial resolution in three dimensions. Honget al. develop a plasmonic ruler based on the fluorescence enhancement of carbon nanotubes on a gold plasmonic substrate, allowing the observation of nanotube endocytosis in three dimensions.
- Guosong Hong
- , Justin Z. Wu
- & Hongjie Dai
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Article
| Open AccessBackbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides
Cell-penetrating peptides can deliver molecular cargoes into living cells, and cross biological membranes by transduction—a non-endocytic mechanism. Here, the transduction efficiency of cyclic arginine-rich peptides is shown to be higher than that of more flexible linear peptides.
- Gisela Lättig-Tünnemann
- , Manuel Prinz
- & M. Cristina Cardoso