Featured
-
-
Article
| Open AccessMonitoring G protein-coupled receptor and β-arrestin trafficking in live cells using enhanced bystander BRET
Cellular signaling processes often involve trafficking of receptors and other proteins between subcellular compartments. Here the authors demonstrate a method based on the concept of Enhanced bystander Bioluminescence Resonance Energy Transfer (EbBRET) that allows efficient real time monitoring of endocytosis and trafficking.
- Yoon Namkung
- , Christian Le Gouill
- & Stéphane A. Laporte
-
Article
| Open AccessPhagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution
Hypoxia induced during inflammation promotes the resolution phase. Here the authors show that the hypoxia results from the respiratory burst in myeloid cells, and induces local EPO production and signaling, which enhances macrophage phagocytosis of debris and migration to draining lymph nodes to promote resolution.
- Bangwei Luo
- , Jinsong Wang
- & Zhiren Zhang
-
Article
| Open AccessFrizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling
PDZ domain-containing proteins are known to function as intracellular scaffolds. Here, Egea-Jimenez et al. report the structure of the tandem PDZ domains of syntenin in complex with a Frizzled 7 peptide and PIP2, show that the ligands bind to syntenin cooperatively and illustrate the role of the complex for Frizzled 7 function.
- Antonio Luis Egea-Jimenez
- , Rodrigo Gallardo
- & Pascale Zimmermann
-
Article
| Open AccessCross-membranes orchestrate compartmentalization and morphogenesis in Streptomyces
Streptomycetes are multicellular bacteria that grow as multinucleoid filaments with infrequent cross-walls. Here, the authors describe a membrane system that forms protein-impermeable barriers and compartmentalizes the multinucleoid filaments independently from the FtsZ-guided cell division machinery.
- Katherine Celler
- , Roman I. Koning
- & Gilles P. van Wezel
-
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
-
Article
| Open AccessGolgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis
Cellulose is produced in plants by cellulose synthase complexes (CSCs) that are assembled in the endomembrane system and then trafficked to the plasma membrane. Here Zhang et al. show that the Golgi-localized STELLO1 and 2 proteins are required for the proper assembly and distribution of CSCs in plant cells.
- Yi Zhang
- , Nino Nikolovski
- & Paul Dupree
-
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
-
Article
| Open AccessPre-40S ribosome biogenesis factor Tsr1 is an inactive structural mimic of translational GTPases
Tsr1 is an essential ribosome biogenesis factor that has known similarity to GTPases. Here, the authors report the Tsr1 crystal structure and show that it is similar to GTPases but that active site residues are not conserved; modelling of the structure into the pre-40S maps allows inferences on ribosomal maturation to be drawn.
- Urszula M. McCaughan
- , Uma Jayachandran
- & Atlanta G. Cook
-
Article
| Open AccessLRP6 acts as a scaffold protein in cardiac gap junction assembly
LRP6 is known for its role as a Wnt co-receptor essential for the canonical Wnt/β-catenin signaling. Here, Li et al. show that LRP6 exerts a Wnt-independent scaffold function and regulates connexin 43 gap junction formation and coupling of cardiomyocytes in mouse hearts.
- Jun Li
- , Changming Li
- & Yi-Han Chen
-
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
-
Article
| Open AccessA vacuole-like compartment concentrates a disordered calcium phase in a key coccolithophorid alga
Coccolithophores are unicellular marine algae that produce calcitic particles inside their cells. Here the authors study cells of the dominant coccolithophore Emiliania huxleyiand identify an intracellular compartment that is filled with high concentrations of a disordered form of calcium.
- Sanja Sviben
- , Assaf Gal
- & André Scheffel
-
Article
| Open AccessMicrotubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion
During tracheal tube fusion in Drosophila, a pair of tip cells form an adherens junction and then fuse their plasma membranes. Here the authors show that a balanced pulling force mediated by myosin and microtubules, as well as localized deposition of matrix, promotes plasma membrane fusion.
- Kagayaki Kato
- , Bo Dong
- & Shigeo Hayashi
-
Article
| Open AccessUnconventional endosome-like compartment and retromer complex in Toxoplasma gondii govern parasite integrity and host infection
The retromer complex is a multi-protein component of the endosomal protein sorting machinery. Here, Sangaré et al. identify unique features in the retromer complex of the parasite Toxoplasma gondii, and show that it is crucial for the biogenesis of secretory organelles in this pathogen.
- Lamba Omar Sangaré
- , Tchilabalo Dilezitoko Alayi
- & Stanislas Tomavo
-
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
-
Article
| Open AccessThree mechanisms control E-cadherin localization to the zonula adherens
E-cadherin is an adhesion molecule mediating cell-cell adhesion; correct localization is important but how localization is controlled is not clear. Here the authors use Drosophilaas a model system to distinguish three distinct trafficking pathways that direct E-cadherin to the zonula adherens.
- Innokenty Woichansky
- , Carlo Antonio Beretta
- & Veit Riechmann
-
Article
| Open AccessFAM21 directs SNX27–retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus
Endosomes maintain cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Here the authors show that the SNX27-retromer-WASH complex acts as a hub to direct cargoes to the plasma membrane by blocking their transport to lysosomes and Golgi apparatus.
- Seongju Lee
- , Jaerak Chang
- & Craig Blackstone
-
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
-
Article
| Open AccessLysosomal recruitment of TSC2 is a universal response to cellular stress
In response to amino acid and growth factor removal the TSC1/2 complex translocates to the lysosome to inactivate mTOR and inhibit cell growth. Here, the authors have shown that other cellular stresses also trigger this translocation to the lysosome suggesting that this is a universal mechanism in the stress response.
- Constantinos Demetriades
- , Monika Plescher
- & Aurelio A. Teleman
-
Article
| Open AccessMembrane potential shapes regulation of dopamine transporter trafficking at the plasma membrane
The dopaminergic system has important roles in a number of cognitive process. Here, the authors use detailed analysis of dopamine transporter trafficking to show its levels at the cell surface are sensitive to changes in membrane potential.
- Ben D. Richardson
- , Kaustuv Saha
- & Habibeh Khoshbouei
-
Article
| Open AccessCLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking
Chloride intracellular channel (CLIC) 4 is an ion channel, localized in the cytoplasm, and first identified as an actin binding protein. Here, Chou et al.knockout CLIC4 in mice and observe tubulogenesis and renal proximal tubule dilation defects, which is caused by irregular actin and endosomal trafficking.
- Szu-Yi Chou
- , Kuo-Shun Hsu
- & Ching-Hwa Sung
-
Article
| Open AccessNovel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion
Anti-Müllerian hormone (AMH) plays a role in sexual differentiation and gonadal function, but extra-gonadal effects of AMH are not known. Here Cimino et al. show that AMH activates a subset of gonadotrophin-releasing hormone (GnRH)-releasing neurons, contributing to luteinizing hormone secretion from the pituitary gland.
- Irene Cimino
- , Filippo Casoni
- & Paolo Giacobini
-
Article
| Open AccessArp2/3-mediated F-actin formation controls regulated exocytosis in vivo
The cytoskeleton plays a crucial role in secretion. Here Tran et al.demonstrate that cortical actin is rearranged at the site of vesicle fusion and recruited to fused secretory granules in Drosophila salivary glands, and show that branched actin nucleators are required for cargo expulsion.
- Duy T. Tran
- , Andrius Masedunskas
- & Kelly G. Ten Hagen
-
Article
| Open AccessDual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis
Rap1, a member of the Ras family of small guanine triphosphatases, mediates lymphocyte adhesion to high endothelial venules. Here the authors show that depending on its activation status Rap1 plays a dual role in T cell adhesion and by regulating T cell homeostasis is involved in the protection from colitis.
- Sayaka Ishihara
- , Akihiko Nishikimi
- & Koko Katagiri
-
Article |
The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis
Munc18-1 binds trans-SNARE complexes and promotes membrane fusion in vitro. Here the authors provide genetic evidence that this trans-SNARE-regulating function plays an essential role in synaptic releases in neurons, and show that this function is disrupted by a disease-causing Munc18-1 mutation.
- Chong Shen
- , Shailendra S. Rathore
- & Jingshi Shen
-
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
-
Article
| Open AccessAutophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity
The MARTX toxin of V. choleraeprocesses itself to deliver three distinct effector domains to the cytosol. Here the authors show that the third effector domain is a phosphatidylinositol-3-phosphate (PtdIns3P)-specific phospholipase that inhibits autophagy in target cells.
- Shivani Agarwal
- , Hyunjin Kim
- & Karla J. F. Satchell
-
Article
| Open AccessSex-specific regulation of follicle-stimulating hormone secretion by synaptotagmin 9
Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) in both male and female mice. Roper et al.show that the synaptotagmin isoform syt-9 is specifically required for FSH secretion, but only in females, revealing a mechanism by which specificity can be encoded in complex secretory cells.
- Lindsey K. Roper
- , Joseph S. Briguglio
- & Edwin R. Chapman
-
Article
| Open AccessPresynaptic spinophilin tunes neurexin signalling to control active zone architecture and function
Synaptic assembly depends on trans-synaptic Neurexin/Neuroligin signalling. Here, Muhammad et al. show that Spinophilin, a pre-synaptic scaffolding protein, interacts with Neurexin, in competition with Syd-1, to regulate the formation and function of synaptic active zones at Drosophilaneuromuscular junctions.
- Karzan Muhammad
- , Suneel Reddy-Alla
- & Stephan J. Sigrist
-
Article
| Open AccessIRSp53 senses negative membrane curvature and phase separates along membrane tubules
The inverted-BAR domain protein IRSp53 associates with the inner leaflet of tubular membranes such as filopodia. Here, Prévostet al. demonstrate that the I-BAR domain of IRSp53 senses negative membrane curvature, and undergoes phase separation which may aid its clustering upon filopodia generation.
- Coline Prévost
- , Hongxia Zhao
- & Patricia Bassereau
-
Article
| Open AccessPhosphoinositide 3-kinase enables phagocytosis of large particles by terminating actin assembly through Rac/Cdc42 GTPase-activating proteins
Phagocytosis of large (but not small) particles requires PI 3-kinase activity. Here, Schlam et al. show that Rho GTPase-activating proteins are recruited to the phagocytic cup by products of PI 3-kinase, resulting in the local inactivation of Rac and Cdc42 and allowing for the completion of internalization of large particles.
- Daniel Schlam
- , Richard D. Bagshaw
- & Sergio Grinstein
-
Article
| Open AccessWall mechanics and exocytosis define the shape of growth domains in fission yeast
Cell shape is determined by a combination of biochemical regulation and mechanical forces. By imaging the dynamic behaviour of growth regulatory proteins in fission yeast and integrating these data within a mechanical model, Abenza et al. find that exocytosis plays a dominant role in shaping growth domains.
- Juan F. Abenza
- , Etienne Couturier
- & Rafael E. Carazo Salas
-
Article
| Open AccessTwo-photon fluorescence lifetime imaging of primed SNARE complexes in presynaptic terminals and β cells
Synaptic vesicles are held in a fusion-competent state prior to their rapid release, which is thought to depend upon formation of trans-SNARE complexes. Takahashi et al. directly image this primed state using FLIM/FRET, and demonstrate differences in basal SNARE organization between neurons and β cells.
- Noriko Takahashi
- , Wakako Sawada
- & Haruo Kasai
-
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
-
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
-
Article
| Open AccessDirect quantitative detection of Doc2b-induced hemifusion in optically trapped membranes
Membrane fusion in cells is triggered by an increase in Ca2+ and involves SNARE complexes and calcium-sensing proteins, but the mechanism underlying the Ca2+-sensors’ role in fusion remains unclear. Here the authors show in vitro that the Ca2+-sensor Doc2b acts directly on membranes and induces a hemifusion intermediate in the presence of calcium.
- Ineke Brouwer
- , Asiya Giniatullina
- & Alexander J. Groffen
-
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
-
Article
| Open AccessmiR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways
MicroRNAs of the miR-34/449 family initiate formation of multiciliated cells through the suppression of cell cycle genes and Notch. Here the authors show that miR-34/449 also regulate the assembly of an apical actin network necessary for basal body anchoring by regulating the expression of R-Ras.
- Benoît Chevalier
- , Anna Adamiok
- & Brice Marcet
-
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
-
Article
| Open AccessCoupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1
The human serum protein apolipoprotein L1 (APOL1) is taken up by trypanosomes where it triggers cell death, forming pores in endolysosomal membranes. Vanwalleghem et al.show that APOL1 triggers both lysosomal and mitochondrial membrane permeabilization, and that the latter is responsible for trypanolysis.
- Gilles Vanwalleghem
- , Frédéric Fontaine
- & Etienne Pays
-
Article |
Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling
Targetting tumour angiogenesis is a useful strategy to reduce tumour burden; however, the clinical benefits of anti-angiogenetic drugs are modest. Here, the authors show that HGFR signalling, which contributes to tumour angiogenesis, requires Arf6 and that blocking Arf6 can lead to reduced tumour growth in mice.
- Tsunaki Hongu
- , Yuji Funakoshi
- & Yasunori Kanaho
-
Article
| Open AccessIntrinsically disordered proteins drive membrane curvature
Proteins that bend membranes often contain curvature-promoting structural motifs such as wedges or crescent-shaped domains. Busch et al.report that intrinsically disordered domains can also drive membrane curvature and provide evidence that steric pressure driven by protein crowding mediates this effect.
- David J. Busch
- , Justin R. Houser
- & Jeanne C. Stachowiak
-
Article |
Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4
Thrombin is a key proinflammatory protease regulating leukocyte trafficking at sites of vascular injury. Here the authors show that balanced thrombin interactions with platelet proteins PAR4, GPIbα and fibrin plays a major role in regulating this process.
- Zane S. Kaplan
- , Alessandro Zarpellon
- & Shaun P. Jackson
-
Article
| Open AccessSUMOylation of synapsin Ia maintains synaptic vesicle availability and is reduced in an autism mutation
Synapsins anchor synaptic vesicles (SVs) to the actin cytoskeleton to establish the reserve vesicle pool. Here Tanget al. show that SUMOylation of synapsin 1a enhances its interaction with SVs to promote efficient reclustering following stimulation, and a mutation linked to autism and epilepsy leads to defective SUMOylation.
- Leo T. -H. Tang
- , Tim J. Craig
- & Jeremy M. Henley
-
Article
| Open AccessA phosphorylation switch controls the spatiotemporal activation of Rho GTPases in directional cell migration
Directed cell migration requires spatially regulated activity of GTPases Rac1 and RhoA. Here Cao et al. show that growth factor stimulation promotes phosphorylation of tensin-3 and phosphatase and tensin homologue (PTEN) and their association with PI 3-kinase and deleted in liver cancer 1 (DLC1) to regulate GTPase activity.
- Xuan Cao
- , Tomonori Kaneko
- & Shawn S. C. Li
-
Article
| Open AccessTD-60 links RalA GTPase function to the CPC in mitosis
TD-60 (RCC2) structurally resembles a guanine nucleotide exchange factor (GEF), but its target GTPase was unknown. Here Papini et al.show that TD-60 is a GEF for RalA, and that RalA helps to regulate the chromosomal passenger complex and kinetochore–microtubule interactions in mitosis.
- Diana Papini
- , Lars Langemeyer
- & William C. Earnshaw
-
Article |
The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17
ErbB signalling is stimulated by the release of its ligands from the cell surface through metalloproteinase-dependent cleavage. Dombernowsky et al. show that this process is controlled by the sorting protein PACS-2, which enhances ErbB ligand release by regulating trafficking of the metalloprotease ADAM17.
- Sarah Louise Dombernowsky
- , Jacob Samsøe-Petersen
- & Marie Kveiborg
-
Article
| Open AccessCell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells
Dendritic cells alternate between fast and slow migratory behaviours, however in the absence of a component of the antigen processing machinery, migration is uniform and fast. Chabaudet al. now show that slow migration results from the relocalisation of myosin II to the cell front where it promotes antigen capture.
- Mélanie Chabaud
- , Mélina L. Heuzé
- & Ana-Maria Lennon-Duménil
-
Article |
The matricellular protein CCN1 mediates neutrophil efferocytosis in cutaneous wound healing
Neutrophils are the first line of response to injury but their persistence can inhibit the resolution phase of tissue repair. Here the authors show that an extracellular matrix protein promotes neutrophil clearance by macrophages, serving as a bridge between the two cell types and speeding up tissue repair.
- Joon-Il Jun
- , Ki-Hyun Kim
- & Lester F. Lau
-
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