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| Open AccessRegulation of lipid saturation without sensing membrane fluidity
Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. Here authors reconstituted the core machinery for regulating lipid saturation in baker’s yeast to directly characterize its response to defined membrane environments and uncover its mode-of-action.
- Stephanie Ballweg
- , Erdinc Sezgin
- & Robert Ernst
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Article
| Open AccessDstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway
Congenital scoliosis is a complex genetic disorder characterized by vertebral malformation. Here, the authors demonstrate that loss of dstyk leads to scoliosis in zebrafish due to dysregulated biogenesis of notochord vacuoles and that DSTYK is required for lysosome biogenesis through mTORC1 regulation.
- Xianding Sun
- , Yang Zhou
- & Lin Chen
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Article
| Open AccessTDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh
Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. Here the authors found that TDP-43, a RNA-binding protein, is required for milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh mRNA stability.
- Limin Zhao
- , Hao Ke
- & Baowei Jiao
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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 AccessQuantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association
Here, using high spatiotemporal resolution light-sheet and fluorescence microscopy, the authors investigate the role of cytoskeletal components on the intracellular transport of Rab11A and influenza virus (IAV) vRNP), and show a preference for Rab11A movement along microtubules that is not essential for IAV vRNP transport.
- Amar R. Bhagwat
- , Valerie Le Sage
- & Seema S. Lakdawala
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Article
| Open AccessTRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKβ/VPS34 pathway
It was known that prolonged TRMPL1 activation induces TFEB translocation and upregulates autophagic gene regulation. Here, the authors show that acute TRMPL1 activation also induces autophagy through VPS34 and by lysosomal calcium release independent of TFEB.
- A. Scotto Rosato
- , S. Montefusco
- & D. L. Medina
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Article
| Open AccessAMPA receptors in the synapse turnover by monomer diffusion
The mechanisms regulating the turnover of the AMPARs in the synapse, which is critically important to sustain basic synaptic activity, remains unclear. In this study, authors used single-molecule imaging techniques to demonstrate that AMPAR tetramers are not stable entities and readily fall apart to dimers and monomers that could reform to tetramers at the synapse, and that rapidly diffusing monomers in the plasma membrane are primarily responsible for the AMPAR turnover in the synapse.
- Jyoji Morise
- , Kenichi G. N. Suzuki
- & Shogo Oka
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Article
| Open AccessQuantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process
How epigenetics coordinate with genetics to impact protein fitness is unknown. Here, using a Variation Spatial Profiling strategy and machine learning, the authors map HDAC impact on a full set of Niemann pick C1 disease variants to quantitate an unanticipated plasticity in central dogma.
- Chao Wang
- , Samantha M. Scott
- & William E. Balch
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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 AccessMiro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery
Mitochondrial cristae organization and ER-mitochondria contact sites are critical structures for cellular function. Here, the authors use super-resolution microscopy to show that Miro GTPases form clusters required for normal ER-mitochondria contact sites formation and to link cristae organization to the mitochondrial transport machinery.
- Souvik Modi
- , Guillermo López-Doménech
- & Josef T. Kittler
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Article
| Open AccessFlotillins promote T cell receptor sorting through a fast Rab5–Rab11 endocytic recycling axis
Internalized receptors are recycled back to the cell surface, but their precise mechanisms are unclear. Here, the authors show that the flotillin membrane proteins may regulate the transfer of internalized T cell receptors into Rab5 and Rab11-positive endosomes to support its rapid recycling.
- Gregory M. I. Redpath
- , Manuela Ecker
- & Jérémie Rossy
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Article
| Open AccessRegulation of the endosomal SNX27-retromer by OTULIN
OTULIN is a linear ubiquitin hydrolase that regulates ubiquitin homeostasis. Here the authors identify the adaptor of the endosomal retromer complex sorting nexin 27 (SNX27) as a binding partner of OTULIN and determine the structure of the OTULIN-SNX27 complex, which reveals a secondary interface through which OTULIN non-catalytically antagonizes SNX27 retromer assembly and cargo loading.
- Aurelia Stangl
- , Paul R. Elliott
- & Daniel Krappmann
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Article
| Open AccessNPC1 regulates ER contacts with endocytic organelles to mediate cholesterol egress
Though endocytosed dietary cholesterol is transferred to the endoplasmic reticulum (ER), how this is regulated is unclear. Here, the authors report a role for Niemann-Pick Type C Protein 1 (NPC1) in tethering endocytic organelles to the ER, which may contribute to interorganelle cholesterol transport.
- D. Höglinger
- , T. Burgoyne
- & E. R Eden
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Article
| Open AccessALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis
Intracellular vesicle transport can be regulated by Brefeldin‐A ADP‐Ribosylated Substrate (BARS) during vesicle fission. Here, the authors show that NADH generated by aldehyde dehydrogenase 7A1 (ALDH7A1) inhibits intracellular transport by targeting BARS and inhibiting COPI vesicle fission during situations of energy deprivation
- Jia-Shu Yang
- , Jia-Wei Hsu
- & Victor W. Hsu
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Article
| Open AccessPituitary cell translation and secretory capacities are enhanced cell autonomously by the transcription factor Creb3l2
Pituitary POMC secreting cells achieve high hormone expression levels after birth but the mechanism for this regulation is unclear. Here, the authors show that this process is driven cell autonomously by the differentiation factor Tpit that activates the bZIP transcription factors Creb3l2 and XBP1 to enhance translation and secretory capacities.
- Konstantin Khetchoumian
- , Aurélio Balsalobre
- & Jacques Drouin
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Article
| Open AccessWHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes
After autophagic cargo degradation, autolysosomes undergo a reformation process to recycle lysosomal membrane components. Here, Dai et al. demonstrate that the actin nucleation promoting factor WHAMM is required for autolysosome reformation by providing an actin scaffold to drive tubulation.
- Anbang Dai
- , Li Yu
- & Hong-Wei Wang
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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 AccessDegron-tagged reporters probe membrane topology and enable the specific labelling of membrane-wrapped structures
Visualising certain organelles and their dynamics is challenging in living cells. Here the authors co-opt selective degradation to label membrane-bound compartments in worm embryos and mammalian cells, revealing membrane topology during cell division.
- Katharina B. Beer
- , Gholamreza Fazeli
- & Ann M. Wehman
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Article
| Open AccessThe late stage of COPI vesicle fission requires shorter forms of phosphatidic acid and diacylglycerol
Phosphatidic acid and diacylglycerol are required for COPI vesicle fission. Here, the authors find that shorter forms of these lipids promote the late stage of COPI vesicle fission, further suggesting how lipid geometry contributes to membrane deformation in driving fission.
- Seung-Yeol Park
- , Jia-Shu Yang
- & Victor W. Hsu
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Article
| Open AccessLysosomal degradation of newly formed insulin granules contributes to β cell failure in diabetes
Impaired beta-cell insulin secretion is a key pathological feature of type 2 diabetes. Here, the authors describe metabolic stress induced lysosomal degradation of newly formed insulin granules, independent of macroautophagy, as a potential mechanism for beta-cell dysfunction.
- Adrien Pasquier
- , Kevin Vivot
- & Romeo Ricci
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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 AccessApoptotic signalling targets the post-endocytic sorting machinery of the death receptor Fas/CD95
Fas is a death receptor that regulates apoptosis in many cell types and is downregulated on the cell surface in many cancers. Here, Sharma et al. show that endosome associated trafficking regulator ENTR1 regulates delivery of Fas to lysosomes, thereby controlling its degradation and signalling.
- Shruti Sharma
- , Antonio Carmona
- & Kai S. Erdmann
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Article
| Open AccessWDFY2 restrains matrix metalloproteinase secretion and cell invasion by controlling VAMP3-dependent recycling
WDFY2 is known as a tumour suppressor but its function is unclear. Here, the authors show that WDFY2 interacts with the v-SNARE VAMP3, leading to a suppression of the metalloprotease MT1-MMP secretion, suggesting that WDFY2 acts a tumour suppressor by suppressing MT1-MMP secretion.
- Marte Sneeggen
- , Nina Marie Pedersen
- & Kay Oliver Schink
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Article
| Open AccessTethering of vesicles to the Golgi by GMAP210 controls LAT delivery to the immune synapse
The immune synapse at the interface between T cells and antigen-presenting cells manifests intense vesicular trafficking, but how the vesicles are sorted is still unclear. Here the authors show that, in activated T cells, the Golgin GMAP210 specifically conveys LAT+ vesicles to immune synapse allowing proper T cell activation.
- Andres Ernesto Zucchetti
- , Laurence Bataille
- & Claire Hivroz
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Article
| Open AccessA protein complex required for polar growth of rhizobial infection threads
Many legumes accommodate rhizobial symbionts via transcellular infection threads. Here the authors show that in Medicago root hairs, polar growth of the infection thread requires a tip-localized protein complex consisting of VPY and VPY-like proteins that are stabilized by the E3 ligase LIN, as well as an exocyst complex subunit.
- Cheng-Wu Liu
- , Andrew Breakspear
- & Jeremy D. Murray
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Perspective
| Open AccessThe role of PS 18:0/18:1 in membrane function
There are several lines of evidence for interactions between the two membrane leaflets in cells. In this review the authors discuss the transmembrane coupling of lipids, the involvement of phosphatidyl serine species PS 18:0/18:1, and their importance for various cellular processes.
- Tore Skotland
- & Kirsten Sandvig
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Article
| Open AccessStructural basis for the homotypic fusion of chlamydial inclusions by the SNARE-like protein IncA
Chlamydia trachomatis forms membrane-bound inclusions inside the host cell that are decorated with IncA, a SNARE-like protein that promotes the fusion of inclusions. Here, Cingolani et al. show that the protein folds into a non-canonical four-helix bundle and identify an intramolecular clamp required for membrane fusion.
- Gino Cingolani
- , Michael McCauley
- & Fabienne Paumet
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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 AccessSORLA regulates endosomal trafficking and oncogenic fitness of HER2
The EGF receptor HER2 is an oncogene protein thought to reside at the plasma membrane, but its endosomal trafficking is currently unclear. Here, the authors report that HER2 is endocytosed and that sortillin-related receptor 1 (SORLA) promotes endosomal HER2 recycling and HER2 oncogenic signalling.
- Mika Pietilä
- , Pranshu Sahgal
- & Johanna Ivaska
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Article
| Open AccessAnchoring cortical granules in the cortex ensures trafficking to the plasma membrane for post-fertilization exocytosis
Mammalian eggs require a single sperm for viable fertilization, and cortical granule exocytosis prevents additional sperm binding. Vogt et al. image at single granule resolution to document that cortical granule anchoring in the cortex ensures proper trafficking, exocytosis and polyspermy block.
- Edgar-John Vogt
- , Keizo Tokuhiro
- & Jurrien Dean
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Article
| Open AccessZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes
Complement activation contributes to vascular inflammation in the contexts of allograft rejection and connective tissue disease. Here Fang et al. identify ZFYVE21 as a novel effector of Rab5 and find it regulates pro-inflammatory NF-κB signaling in endothelial cells in response to complement activation.
- Caodi Fang
- , Thomas D. Manes
- & Dan Jane-wit
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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 AccessSTX17 dynamically regulated by Fis1 induces mitophagy via hierarchical macroautophagic mechanism
Mitophagy plays a critical role in cellular homeostasis, and PINK1/Parkin-mediated mitophagy is the most thoroughly characterized. Here, Xian et al. show that STX17 induces mitophagy via a macroautophagy pathway regulated by Fis1, by a PINK1/Parkin-independent route.
- Hongxu Xian
- , Qiaoyun Yang
- & Yih-Cherng Liou
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Article
| Open AccessDystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells
Caveolae are mechanosensors and mutations of their coat proteins are implicated in muscle disorders, but molecular mechanisms are unclear. Here, the authors show that caveolae can regulate IL6/STAT3 signaling in muscle cells under stress, and that dystrophy related Cav3 mutant myotubes have reduced caveolae and upregulated IL6 signaling.
- Melissa Dewulf
- , Darius Vasco Köster
- & Cedric M. Blouin
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Article
| Open AccessVps11 and Vps18 of Vps-C membrane traffic complexes are E3 ubiquitin ligases and fine-tune signalling
Endosomal fusion depends on the HOPS and CORVET complexes but whether and how their subunits modulate signal transduction is not fully understood. Here, the authors show that the HOPS/CORVET subunits Vps11 and Vps18 are E3 ubiquitin ligases that are involved in the regulation of ERα signalling.
- Gregory Segala
- , Marcela A. Bennesch
- & Didier Picard
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Article
| Open AccessKIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a
Exosomes are intercellular signaling vesicles created by fusion of multivesicular bodies (MVBs) and the plasma membrane (PM), but secretory regulation is ill-defined. Song et al. show that KIBRA controls exosome secretion by protecting Rab27a from proteasomal degradation, promoting MVB-PM docking.
- Lin Song
- , Shi Tang
- & Yifeng Du
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Article
| Open AccessSNAREs define targeting specificity of trafficking vesicles by combinatorial interaction with tethering factors
Intracellular vesicle targeting is mediated by Rab GTPases that cooperate with phosphatidylinositides and SNARE proteins, which then facilitate membrane fusion. Here, the authors microinject artificial vesicles into HeLa cells and find that SNAREs play a more prominent role in targeting specificity of trafficking vesicles than previously known.
- Seiichi Koike
- & Reinhard Jahn
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Article
| Open AccessClassification of the human phox homology (PX) domains based on their phosphoinositide binding specificities
Phox homology (PX) domains are membrane interacting domains that bind to various lipids. Here authors screen all human PX domains systematically for their phospholipid preferences and define four classes and provide the basis for defining and predicting functional PX-membrane interactions.
- Mintu Chandra
- , Yanni K.-Y. Chin
- & Brett M. Collins
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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
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Article
| Open AccessUSP32 regulates late endosomal transport and recycling through deubiquitylation of Rab7
Though ubiquitin is known to broadly influence endosomal trafficking, few ubiquitin-utilizing enzymes targeting endosomal regulators are known. Here, the authors find that the deubiquitylating enzyme (DUB) USP32 influences endosomal membrane dynamics by deubiquitinating Rab7.
- Aysegul Sapmaz
- , Ilana Berlin
- & Huib Ovaa
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Article
| Open AccessSulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A
Extracellular vesicles are released from cells and permit communication between different cell types. Here, the authors identify that the FDA approved antibiotic sulfisoxazole, can block the release of these vesicles in breast cancer cells resulting in reduced cell growth in vitro and in vivo.
- Eun-Ju Im
- , Chan-Hyeong Lee
- & Moon-Chang Baek
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Article
| Open AccessA TonB-dependent transporter is required for secretion of protease PopC across the bacterial outer membrane
TonB-dependent transporters (TBDTs) are outer membrane proteins that import nutrients and bacteriocins in bacteria. Here, Gómez-Santos et al. show that a TBDT is required for secretion of a protease in Myxococcus xanthus, suggesting that some TBDTs may be involved in protein secretion.
- Nuria Gómez-Santos
- , Timo Glatter
- & Lotte Søgaard-Andersen
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Article
| Open AccessThe Caspase-3 homolog DrICE regulates endocytic trafficking during Drosophila tracheal morphogenesis
Caspases are well-known drivers of apoptosis, although recent studies suggest potential non-apoptotic functions. Here, McSharry and Beitel show that the Drosophila executioner caspase DrICE regulates endocytic trafficking of key proteins downstream of Hippo during tracheal morphogenesis.
- Saoirse S. McSharry
- & Greg J. Beitel
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Article
| Open AccessKDEL receptor regulates secretion by lysosome relocation- and autophagy-dependent modulation of lipid-droplet turnover
Inter-organelle signaling coordinates adaptive responses via currently unknown mechanisms. Here, Tapia et al. show that KDEL signaling repositions lysosomes in a complex process termed ‘traffic-induced degradation response for secretion’ (TIDeRS) that connects multiple pathways and Golgi secretion.
- Diego Tapia
- , Tomás Jiménez
- & Jorge Cancino
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Article
| Open AccessBMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis
BMP ligands act as retrograde signalling molecules to regulate presynaptic development, and regulation of BMP receptors by endocytosis may be an important component of this signalling pathway. Here, the authors show that Abi-mediated macropinocytosis of BMP receptors in Drosophila larva and contributes to neuromuscular development.
- Najin Kim
- , Sungdae Kim
- & Seungbok Lee
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Article
| Open AccessInvestigation of F-BAR domain PACSIN proteins uncovers membrane tubulation function in cilia assembly and transport
PACSIN proteins are known to mediate membrane tubulation. Here the authors show that PACSIN - positive membranous tubules extend from the ciliary pocket membrane and during ciliogenesis from the ciliary vesicle to the plasma membrane, called extracellular membrane channels (EMCs).
- Christine Insinna
- , Quanlong Lu
- & Christopher J. Westlake
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Article
| Open AccessCorrelative cryo-electron microscopy reveals the structure of TNTs in neuronal cells
The architecture of functional TNTs is still under debate. Here, the authors combine correlative FIB-SEM, light- and cryo-electron microscopy approaches to elucidate the structure of TNTs in neuronal cells, showing that they form structures that are distinct form other membrane protrusions.
- Anna Sartori-Rupp
- , Diégo Cordero Cervantes
- & Chiara Zurzolo
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Article
| Open AccessGORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation
COPI is recruited to the membrane by binding to Arf GTPases. Here the authors find that GORAB, a trans-Golgi protein, promotes COPI recruitment by forming membrane domains that also contain the COPI-interacting protein Scyl1, which is required for efficient glycosylation of cargo proteins.
- Tomasz M. Witkos
- , Wing Lee Chan
- & Martin Lowe
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Article
| Open AccessMunc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
Synaptic exocytosis depends on formation of the SNARE complex but its assembly mechanism is still under debate. Here, the authors identify an interaction between Munc13-1 and synaptobrevin-2 that is critical for the transition of the Munc18-1/syntaxin-1 complex to the SNARE complex.
- Shen Wang
- , Yun Li
- & Cong Ma