Featured
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| Open AccessEndocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation
Growth factors rapidly raise cellular glycolysis. Here, authors unveil a mechanism where RTK/GLUT1-containing endocytic vesicles deliver glucose to glycolytic enzymes near mitochondria without upregulating cell surface glucose transporters.
- Ryouhei Tsutsumi
- , Beatrix Ueberheide
- & Yoshiro Saito
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Article
| Open AccessAdhesion energy controls lipid binding-mediated endocytosis
Many bacterial toxins and viruses deform membranes prior to entering cells via clathrin independent endocytosis. Here the authors show that multivalent lipid binding by globular particles can exceed a threshold adhesion energy required for membrane deformation and that this is sufficient for internalization.
- Raluca Groza
- , Kita Valerie Schmidt
- & Helge Ewers
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Article
| Open AccessThe proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration
In the kidney, maintaining permeability of the filtration barrier is critical. Here, Sachs W. et al show that homeostasis of podocytes and glomerular endothelial cells relies on differing proteasome constitutions which orchestrate endocytic activity in addition to protein degradation.
- Wiebke Sachs
- , Lukas Blume
- & Catherine Meyer-Schwesinger
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Perspective
| Open AccessMembrane transformations of fusion and budding
Life-crucial membrane fusion and budding were traditionally viewed with electron microscopy. With recent breakthroughs that visualize membrane transformation in real time, Wu and Chan synthesize a new model with mechanistic principles and functions.
- Ling-Gang Wu
- & Chung Yu Chan
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Article
| Open AccessSelf-assembly of CIP4 drives actin-mediated asymmetric pit-closing in clathrin-mediated endocytosis
CIP4 drives an asymmetric closing process in clathrin-mediated endocytosis by LLPS-driven self assembly and stereospecific interaction with the curved membrane and actin-regulating proteins which generates an actin-rich microenvironment near the pit.
- Yiming Yu
- & Shige H. Yoshimura
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Article
| Open AccessMembrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis
The authors describe the mechanism of exo-endocytosis coupling at synapses. They find that actin forms a ring around the region of exocytosis. This ring conserves membrane area, allowing induction of inward membrane buckling following exocytosis.
- Tyler H. Ogunmowo
- , Haoyuan Jing
- & Jian Liu
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Article
| Open AccessStable endocytic structures navigate the complex pellicle of apicomplexan parasites
Apicomplexan parasites share complex cell pellicular structures that isolates the cytosol from most of the plasma membrane. Koreny et al show that, as an early adaptation to this barrier, dedicated stable endocytic structures occur at select sites in these cells. In Toxoplasma, plasma membrane homeostasis is particularly dependent on endocytosis.
- Ludek Koreny
- , Brandon N. Mercado-Saavedra
- & Ross F. Waller
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Article
| Open AccessCell surface protein aggregation triggers endocytosis to maintain plasma membrane proteostasis
How cells respond to denaturation of extracellular protein domains remained largely unknown. Here, authors describe an aggregation-dependent endocytosis pathway, facilitating uptake and degradation of antibody- and stress-induced protein aggregates.
- David Paul
- , Omer Stern
- & Harvey McMahon
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Article
| Open AccessA conformational switch in clathrin light chain regulates lattice structure and endocytosis at the plasma membrane of mammalian cells
Conformational changes within proteins are thought to regulate clathrin-mediated endocytosis. Here, authors develop a correlative FRET and EM imaging method and uncover a structural switch in clathrin light chain that controls endocytosis in cells.
- Kazuki Obashi
- , Kem A. Sochacki
- & Justin W. Taraska
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Article
| Open AccessDifferent pathways for engulfment and endocytosis of liquid droplets by nanovesicles
In this work, the authors investigate on how condensate droplets, arising from liquid-liquid phase separation, can be engulfed by nanovesicles via distinct pathways, leading to different vesicle-droplet morphologies. Two key parameters are the stress asymmetry of the vesicle membrane and the line tension of the contact line between vesicle and droplet.
- Rikhia Ghosh
- , Vahid Satarifard
- & Reinhard Lipowsky
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Article
| Open AccessThe molecular organization of differentially curved caveolae indicates bendable structural units at the plasma membrane
Caveolae can bend and flatten, but how this is regulated is not well understood. Authors use correlative super-resolution light and electron microscopy to map the key proteins that mediate curvature of the caveolar coat.
- Claudia Matthaeus
- , Kem A. Sochacki
- & Justin W. Taraska
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Article
| Open AccessSpatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival
Recruitment of Receptor Tyrosine Kinase signalling partners during endocytosis, specifically during recycling to the plasma membrane, is crucial to signal propagation and regulation. Here, the authors reveal FGFR signalling partners proximal to recycling endosomes with a spatially resolved phosphoproteomics approach.
- Joanne Watson
- , Harriet R. Ferguson
- & Chiara Francavilla
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Article
| Open AccessActin polymerization promotes invagination of flat clathrin-coated lattices in mammalian cells by pushing at lattice edges
The role of actin filaments in clathrin-mediated endocytosis (CME) is unclear. Here, Yang et al. show that branched actin filaments promote CME by pushing on clathrin coat edges in an epsin-dependent manner, dividing large flat clathrin plaques into sizes that facilitate invagination.
- Changsong Yang
- , Patricia Colosi
- & Tatyana Svitkina
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Article
| Open AccessEndocytosis-like DNA uptake by cell wall-deficient bacteria
Horizontal gene transfer in bacteria can occur through mechanisms such as conjugation, transduction and transformation, which facilitate the passage of DNA across the cell wall. Here, Kapteijn et al. show that cell wall-deficient bacteria can take up DNA and other extracellular materials via an endocytosis-like process.
- Renée Kapteijn
- , Shraddha Shitut
- & Dennis Claessen
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Article
| Open AccessMultivalent interactions between molecular components involved in fast endophilin mediated endocytosis drive protein phase separation
Here the authors show that protein phase separation is a key mechanism in cellular receptor internalization via fast endophilin mediated endocytosis (FEME). Phase separation facilitates multivalent FEME-protein assembly in this clathrin-independent pathway.
- Samsuzzoha Mondal
- , Karthik Narayan
- & Tobias Baumgart
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Article
| Open AccessSynaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis
How pancreatic islets of Langerhans are built during development is incompletely understood. Here the authors find that Synaptotagmin-13 mediates remodeling of cell-matrix adhesion to regulate endocrine cell egression and islet morphogenesis.
- Mostafa Bakhti
- , Aimée Bastidas-Ponce
- & Heiko Lickert
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Article
| Open AccessNeuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability
Functional vascular tree formation is a key step in many contexts, such as cancer, and Neuropilin1 (NRP1) has been associated with adhesion receptor endocytic turnover. Here, authors show NRP1 and its mini-WARS ligand play a role in reducing endothelial permeability.
- Noemi Gioelli
- , Lisa J. Neilson
- & Guido Serini
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Article
| Open AccessMolecular mechanics underlying flat-to-round membrane budding in live secretory cells
Shin et al. report the molecular mechanics of membrane budding: actin and dynamin pull membrane inward to form a Λ-shape profile; dynamin helices convert Λ- to Ω-shape by constricting Λ’s base, and then constrict Ω-profile’s pore to form a vesicle.
- Wonchul Shin
- , Ben Zucker
- & Ling-Gang Wu
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Article
| Open AccessBranched actin networks are organized for asymmetric force production during clathrin-mediated endocytosis in mammalian cells
Drubin et al. use three different advanced imaging approaches to show that actin assembles preferentially at stalled clathrin-mediated endocytosis sites, where the actin pulls vesicles into the cell asymmetrically, as a bottle opener pulls off a cap.
- Meiyan Jin
- , Cyna Shirazinejad
- & David G. Drubin
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Article
| Open AccessThe PripA-TbcrA complex-centered Rab GAP cascade facilitates macropinosome maturation in Dictyostelium
Macropinocytosis has emerged as an evolutionarily conserved mechanism for bulk uptake of extracellular fluid. Here they show how a Rab GAP cascade centered on the PripA-TbcrA complex facilitates Rab conversion and macropinosome maturation.
- Hui Tu
- , Zhimeng Wang
- & Huaqing Cai
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Article
| Open AccessImaging vesicle formation dynamics supports the flexible model of clathrin-mediated endocytosis
Despite decades of research, the dynamics of clathrin-coated vesicle formation is ambiguous. Here, authors use STAR microscopy to quantify the nanoscale dynamics of vesicle formation, supporting the flexible model of clathrin-mediated endocytosis.
- Tomasz J. Nawara
- , Yancey D. Williams II
- & Alexa L. Mattheyses
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Article
| Open AccessDual clathrin and integrin signaling systems regulate growth factor receptor activation
The integration and organization of growth factor signaling, adhesion, and endocytosis is poorly understood. Here the authors use light and electron microscopy to shed light on the role of flat clathrin lattices and cell adhesion in growth factor signaling.
- Marco A. Alfonzo-Méndez
- , Kem A. Sochacki
- & Justin W. Taraska
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Article
| Open AccessLung emphysema and impaired macrophage elastase clearance in mucolipin 3 deficient mice
Excess macrophage elastase MMP-12 is a major driver of chronic obstructive pulmonary disease. Here the authors show that the endolysosomal ion channel TRPML3 is a regulator of the cellular reuptake of MMP-12, thus neutralizing harmful MMP-12 in the lung.
- Barbara Spix
- , Elisabeth S. Butz
- & Christian Grimm
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Article
| Open AccessThe phosphoinositide coincidence detector Phafin2 promotes macropinocytosis by coordinating actin organisation at forming macropinosomes
Macropinocytosis permits the cellular uptake of fluids and nutrients via macropinosomes. Here, the authors show that Phafin2 is required for the formation of macropinosomes and permits their transit through dense actin networks.
- Kay Oliver Schink
- , Kia Wee Tan
- & Harald Stenmark
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Article
| Open AccessCryoEM structure of the super-constricted two-start dynamin 1 filament
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
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Article
| Open AccessTMEM16F and dynamins control expansive plasma membrane reservoirs
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
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Article
| Open AccessThe structural dynamics of macropinosome formation and PI3-kinase-mediated sealing revealed by lattice light sheet microscopy
Macropinocytosis is a cellular process for the uptake of extracellular fluid. Here, the authors use lattice light sheet microscopy to examine the spatial dynamics of the plasma membrane, PI3K activity, and structural differences of various macrophage cell types during macropinocytosis.
- Shayne E. Quinn
- , Lu Huang
- & Brandon L. Scott
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Article
| Open AccessCD13 orients the apical-basal polarity axis necessary for lumen formation
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
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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
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Article
| Open AccessStructure of the endocytic adaptor complex reveals the basis for efficient membrane anchoring during clathrin-mediated endocytosis
During clathrin-mediated endocytosis in yeast, endocytic coat adaptors, Sla2 and Ent1, must remain attached to the plasma membrane to transmit force from the actin cytoskeleton required for membrane invagination. Here authors present a cryo-EM structure of a 16-mer complex of the ANTH and ENTH membrane-binding domains from Sla2 and Ent1 bound to PIP2 that constitutes the anchor to the plasma membrane.
- Javier Lizarrondo
- , David P. Klebl
- & Maria M. Garcia-Alai
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Article
| Open AccessHuman FCHO1 deficiency reveals role for clathrin-mediated endocytosis in development and function of T cells
FCH domain only 1 (FCHO1) is a key molecule involved in clathrin-mediated endocytosis (CME). Here, the authors report homozygous FCHO1 mutations in individuals with variable T and B cell lymphopenia, which are associated with loss-of-function of FCHO1 and impaired formation of clathrin-coated pits in T cells.
- Marcin Łyszkiewicz
- , Natalia Ziętara
- & Christoph Klein
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Article
| Open AccessMacropinocytosis drives T cell growth by sustaining the activation of mTORC1
Macropinocytosis has been implicated in the expansion of transformed cells when nutrient-depleted. Here the authors show that macropinocytosis also contributes to the expansion of primary T cells even under nutrient-replete conditions, potentially by providing access of extracellular amino acids to an endolysosomal compartment to sustain mTORC1 activation.
- John C. Charpentier
- , Di Chen
- & Philip D. King
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Article
| Open AccessForces during cellular uptake of viruses and nanoparticles at the ventral side
Many intracellular pathogens mimic extracellular matrix motifs to specifically interact with the host membrane which may influences virus particle uptake. Here authors use single molecule tension sensors to reveal the minimal forces exerted on single virus particles and demonstrate that the uptake forces scale with the adhesion energy.
- Tina Wiegand
- , Marta Fratini
- & Joachim P. Spatz
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Article
| Open AccessClathrin light chain A drives selective myosin VI recruitment to clathrin-coated pits under membrane tension
Clathrin light chains (CLCa and CLCb) are major constituents of clathrin-coated vesicles. Here authors find and structurally characterize the selective interaction between CLCa and the actin motor protein myosin VI which act together to generate the force that leads to invagination and fission at the apical surface.
- Matteo Biancospino
- , Gwen R. Buel
- & Simona Polo
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Article
| Open AccessCellular internalization of bystander nanomaterial induced by TAT-nanoparticles and regulated by extracellular cysteine
To enter the cells, nanomaterials often need covalent conjugation with cell-penetrating ligands such as TAT. Here, the authors show that simple mixing with TAT-coupled nanoparticles enables the cellular uptake of unfunctionalized nanoparticles, and its activity is stimulated by cysteine in the medium.
- Yushuang Wei
- , Tang Tang
- & Hong-Bo Pang
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Article
| Open AccessDopey1-Mon2 complex binds to dual-lipids and recruits kinesin-1 for membrane trafficking
Proteins are transported among eukaryotic organelles along the cytoskeleton in membrane carriers. Here authors find that the Dopey1-Mon2 complex functions as a dual-lipid-regulated cargo-adaptor to recruit kinesin-1 to secretory and endocytic organelles or membrane carriers.
- Divyanshu Mahajan
- , Hieng Chiong Tie
- & Lei Lu
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Article
| Open AccessActomyosin-driven force patterning controls endocytosis at the immune synapse
The immune synapse promotes cellular information exchange but the role of biophysical forces in synapse function is unclear. Here, the authors show that B cells exert two types of forces, a centripetal myosin II-driven force and a central actin protrusive force at the site of antigen extraction.
- Anita Kumari
- , Judith Pineau
- & Paolo Pierobon
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Article
| Open AccessEndophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis
VEGF-A/VEGFR2 signaling is a key driver of endothelial cell migration during sprouting angiogenesis. Here Genet et al. show that endophilin A2 regulates these processes by mediating clathrin-independent VEGFR2 internalization.
- Gael Genet
- , Kevin Boyé
- & Anne Eichmann
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Article
| Open AccessWASH phosphorylation balances endosomal versus cortical actin network integrities during epithelial morphogenesis
The regulation and coordination of F-actin networks are not well understood. Here, the authors show an antagonistic relationship between endosomal F-actin assembly and cortical bundle integrity during epithelial tube maturation that is regulated by kinase and phosphatase activity modifying WASH.
- Vasilios Tsarouhas
- , Dan Liu
- & Christos Samakovlis
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Article
| Open AccessMitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling
The mechanisms promoting insulin resistance at the receptor level are poorly understood. Here, Choi et al. show that mitotic proteins and the SHP2-MAPK pathway regulate receptor endocytosis and insulin signaling feedback, identifying a potential role for SHP2 inhibitors to treat diabetes.
- Eunhee Choi
- , Sotaro Kikuchi
- & Hongtao Yu