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Salmonella exploits membrane reservoirs for invasion of host cells
The plasma membrane of eukaryotic cells can fold inwards to create reservoirs that store or release excess membrane. Zhu et al. show that Salmonella-secreted effectors modulate these reservoirs to facilitate host cell invasion.
- Hongxian Zhu
- , Andrew M. Sydor
- & John H. Brumell
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Article
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LDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments
The mechanisms transporting fatty acids into the cell are not completely understood. Here, the authors discover a selective transporter for a specific class of lipids, and show its role in regulating neutrophil function during myocardial ischemia-reperfusion injury.
- Wenwen Tang
- , Yi Luan
- & Dianqing Wu
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Article
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Endocytic 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
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Adhesion 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
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Pheromone-based communication influences the production of somatic extracellular vesicles in C. elegans
Extracellular vesicles are fundamental in cellular communication. Here, authors show how C. elegans pheromones regulate vesicle production, showcasing the impact of social behaviors on cellular mechanisms.
- Agata Szczepańska
- , Katarzyna Olek
- & Michał Turek
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Article
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Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP2-mediated endocytosis
PI3 kinase is known to promote cell migration through its catalytic activity. Here, the authors show that the kinase also induces endocytosis through a non-catalytic pathway that actually decreases migratory speed and persistence, revealing a more subtle regulation of motility.
- Hideaki T. Matsubayashi
- , Jack Mountain
- & Takanari Inoue
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Article
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SNX8 enables lysosome reformation and reverses lysosomal storage disorder
Lysosomal storage disorders (LSDs) are severe genetic diseases currently without routine therapies. Here, the authors identified that SNX8 participates in lysosome reformation and serves as a potential drug target for new therapies to treat LSDs.
- Xinran Li
- , Cong Xiang
- & Xin-Hua Feng
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Matters Arising
| Open AccessDoes the KDEL receptor cycle between the Golgi and the ER?
- Fernando Aniento
- & David G. Robinson
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Article
| Open Access
Rab GTPases and phosphoinositides fine-tune SNAREs dependent targeting specificity of intracellular vesicle traffic
Targeting of transport vesicles requires specific proteins and membrane lipids. Here, authors microinjected liposomes with a predetermined composition to show that targeting by SNAREs is refined when polyphosphoinositides and Rab GTPases are included.
- Seiichi Koike
- & Reinhard Jahn
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Article
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TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry
How RNA polymerase II subunits enter the nucleus is not well understood. Here, the authors show that Transport and Golgi organization protein 6, TANGO6, recruits RNA polymerase II subunit B2, RPB2, to the ER membrane in a retrograde manner and transports it to the nucleus with the aid of importins.
- Zhi Feng
- , Shengnan Liu
- & Li Li
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Article
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RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling
Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that primarily responds to ligation of bacterial lipopolysaccharide. Here the authors suggest the intramembrane protease RHBDL4 as a regulator of TLR4 signaling.
- Julia D. Knopf
- , Susanne S. Steigleder
- & Marius K. Lemberg
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Article
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Chloride intracellular channel (CLIC) proteins function as fusogens
The Chloride Intracellular Channel (CLIC) protein family is highly conserved, yet their function remains a matter of ongoing research. Here, authors reveal their ability to facilitate membrane fusion, shedding light on their physiological role.
- Bar Manori
- , Alisa Vaknin
- & Yoni Haitin
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Article
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SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle
SARS-CoV-2 uses the host endolysosomal system for replication and egress. Here the authors show that SARS-CoV-2 virulence factor ORF3a localizes to the late endocytic compartments of the host cell to disrupt Rab7 GTP to GDP cycling and block lysosome function in cargo degradation, while activated Rab7 promotes virus replication.
- Kshitiz Walia
- , Abhishek Sharma
- & Amit Tuli
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Article
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Cytokinetic abscission requires actin-dependent microtubule severing
Completion of cell division requires severing both the microtubules and the plasma membrane that connects daughter cells. Here, the authors show that branched actin regulates ESCRT localization to promote the microtubule cut, which happens before membrane scission.
- Tamara Advedissian
- , Stéphane Frémont
- & Arnaud Echard
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Article
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Structural insight into an Arl1–ArfGEF complex involved in Golgi recruitment of a GRIP-domain golgin
Arl1 is a GTP-binding protein that interacts with the guanine nucleotide exchange factor Gea2 to recruit the golgin Imh1 to the Golgi. Here, the authors report structures of the full-length Gea2 and the Arl1–Gea2 complex, with insights into the mechanism of their function in membrane trafficking.
- H. Diessel Duan
- , Bhawik K. Jain
- & Huilin Li
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Article
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The 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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Article
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Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1
Structural and functional studies highlight the molecular regulation of assembling the mitochondrial division machinery. The core unit is closed, and specific interactions open this unit to facilitate assembly at the right place and time in cells.
- Kristy Rochon
- , Brianna L. Bauer
- & Jason A. Mears
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Article
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In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography
Actin mediates insulin secretion in pancreatic β-cells through remodeling. Here, authors report the in situ structure of actin remodeling and quantify changes in architecture, alignment, and interactions during glucose-stimulated insulin secretion.
- Weimin Li
- , Angdi Li
- & Liping Sun
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Article
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Intercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding
The matrix metalloprotease MT1-MMP drives cancer metastasis. Here, the authors demonstrate how invasive cancer cells instigate non-invasive neighbouring cells to become degradative and invasive by transferring catalytically active MT1-MMP fragments.
- Eva Maria Wenzel
- , Nina Marie Pedersen
- & Camilla Raiborg
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Article
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Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen
Shigella enters human cells in a phagocytic vacuole and then escapes the vacuole to colonize the cytosol. Here, Chang and coworkers show that Shigella uses a bacterial effector to subvert host Rab proteins, microtubules and molecular motors to provide mechanical force to facilitate Shigella escape.
- Yuen-Yan Chang
- , Camila Valenzuela
- & John Rohde
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Article
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Phosphoglycerate kinase 1 acts as a cargo adaptor to promote EGFR transport to the lysosome
The epidermal growth factor receptor (EGFR) plays important roles in cell growth and motility. Here, authors reveal an unexpected function for a metabolic enzyme PGK1 and advance the mechanistic understanding of lysosomal transport of EGFR.
- Shao-Ling Chu
- , Jia-Rong Huang
- & Jia-Wei Hsu
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Article
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DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy
Small GTPases such as Rabs control the positioning of lysosomes. Here, the authors unveil a molecular cascade orchestrated by Arl8/DENND6A/Rab34 that regulates lysosome location, impacting autophagy.
- Rahul Kumar
- , Maleeha Khan
- & Peter S. McPherson
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Article
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MARC-3, a membrane-associated ubiquitin ligase, is required for fast polyspermy block in Caenorhabditis elegans
In many sexually reproducing animals, the oocyte fuses with only one sperm during fertilization. Here, the authors show that C. elegans MARC-3, a membrane-associated RING-CH-type ubiquitin ligase, regulates polyspermy block after fertilization and maternal membrane protein degradation during the oocyte-to-embryo transition.
- Ichiro Kawasaki
- , Kenta Sugiura
- & Ken Sato
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Article
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Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol
Stimulator of interferon genes (STING) is known to translocate from ER to Golgi while orchestrating type I interferon responses to DNA. Here, the authors show single-molecule resolution images of STING clustering at the trans-Golgi network, where it acts as a scaffold to trigger downstream signaling.
- Haruka Kemmoku
- , Kanoko Takahashi
- & Tomohiko Taguchi
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Article
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Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation
A vesicle trafficking Rab11 effector switch is important for ciliogenesis. Here, the authors report a ciliopathy-related disorder caused by variants in WDR44, a Rab11 effector. WDR44 variants show higher affinity for Rab11 and can impair ciliogenesis.
- Andrea Accogli
- , Saurabh Shakya
- & Christopher J. Westlake
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Article
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A role and mechanism for redox sensing by SENP1 in β-cell responses to high fat feeding
Insulin secretion adapts to metabolic needs, but how this happens over the short term is not clear. Here the authors show this involves upregulation of beta-cell exocytosis and requires the SUMO-protease SENP1, which responds to redox state in a zinc-dependent manner.
- Haopeng Lin
- , Kunimasa Suzuki
- & Patrick E. MacDonald
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Perspective
| Open Access
Membrane 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
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Ubiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast wtf meiotic drivers
Meiotic drivers of the wtf family kill progeny lacking the driver by producing a toxin and an antidote. Here, authors reveal that ubiquitination-mediated sorting of the antidote prevents it from becoming toxic and enables it to neutralize the toxin.
- Jin-Xin Zheng
- , Tong-Yang Du
- & Li-Lin Du
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Article
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Nutrient deprivation alters the rate of COPII subunit recruitment at ER subdomains to tune secretory protein transport
Movement of secretory cargoes from the endoplasmic reticulum relies on the COPII protein complex. Here, authors combine gene editing technology with state-of-the-art fluorescence microscopy to define the native dynamics of COPII recruitment at ER subdomains for the first time.
- William Kasberg
- , Peter Luong
- & Anjon Audhya
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Article
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Nanobody-based VSR7 tracing shows clathrin-dependent TGN to Golgi recycling
Nanobody-epitope interaction-based analysis of the Arabidopsis VACUOLAR SORTING RECEPTOR7 (VSR7) suggests immobilization-based ligand transport to the TGN/EE and ends due to acidity-driven ligand release and clathrin-dependent receptor recycling.
- Xiaoyu Shao
- , Hao Xu
- & Peter Pimpl
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Article
| Open Access
A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
The molecular mechanism by which exosomes are released from cells is unclear. Here the authors report that a phosphatidylinositide conversion couples the recruitment of the octameric exocyst complex to multivesicular endosomes for exosome secretion.
- Di-Ao Liu
- , Kai Tao
- & Wei Guo
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Article
| Open Access
Synapsin condensation controls synaptic vesicle sequestering and dynamics
Brain functioning critically relies on coordinated neurotransmitter release by synaptic vesicles (SVs) at synapses. This study shows that synapsin/SVs condensation is sufficient to guarantee reliable confinement and motility of SVs at synapses in vivo.
- Christian Hoffmann
- , Jakob Rentsch
- & Dragomir Milovanovic
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Article
| Open Access
C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane tethering and fusion in mammalian autophagy
The HOPS complex mediates membrane tethering and autophagosome-lysosome fusion. Here, the authors biochemically reconstitute the mammalian HOPS in protoliposomes and propose a model of complex assembly that depends on Rab2 and Rab39A.
- Shen Zhang
- , Mindan Tong
- & Qing Zhong
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Article
| Open Access
Rab41-mediated ESCRT machinery repairs membrane rupture by a bacterial toxin in xenophagy
Xenophagy targets cytosolic bacteria, but their membrane homeostatic system is not known. Here the authors show that the ESCRT machinery repairs xenophagic membrane damaged by a bacterial toxin, which is regulated by the TOM1L2–Rab41 that recruits VPS4.
- Takashi Nozawa
- , Hirotaka Toh
- & Ichiro Nakagawa
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Article
| Open Access
The TNFR Wengen regulates the FGF pathway by an unconventional mechanism
Mechanistic studies of receptor action have aided our understanding of developmental processes and facilitated drug development. Here they show that the TNFR-Wengen acts by forming a complex with the FGFR-Breathless, regulating its activity during cell differentiation in the developing respiratory system of Drosophila.
- Annalisa Letizia
- , Maria Lluisa Espinàs
- & Marta Llimargas
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Article
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A mechanism that ensures non-selective cytoplasm degradation by autophagy
How membrane morphology is regulated during autophagosome formation remains elusive. Here, authors reveal a mechanism by which the forming autophagosomal membrane expands with a large opening for non-selective sequestration of the cytoplasm.
- Tetsuya Kotani
- , Yuji Sakai
- & Hitoshi Nakatogawa
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Article
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Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation
The molecular mechanism of syncytium formation during SARS-CoV-2 infection is not fully understood. Zhang et al. now show that cell surface heparan sulfate enhances spike-induced ACE2 clustering and cell-cell fusion, which depends on a conserved ACE2 linker and is blocked by a heparan sulfate binding drug.
- Qi Zhang
- , Weichun Tang
- & Yihong Ye
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Article
| Open Access
The tectonic complex regulates membrane protein composition in the photoreceptor cilium
The photoreceptor cilium contains an exclusive group of proteins responsible for capturing light and eliciting a visual response. Here, the authors show that the tectonic complex plays a role in the barrier that prevents unsolicited protein entry into the cilium.
- Hanh M. Truong
- , Kevin O. Cruz-Colón
- & Jillian N. Pearring
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Article
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Deep and fast label-free Dynamic Organellar Mapping
Regulated subcellular localization changes control protein function. Here, the authors provide a seamless spatial proteomics pipeline for mapping whole-cell protein localization dynamics, which includes a scalable workflow and a software suite for automated data analysis and visualization.
- Julia P. Schessner
- , Vincent Albrecht
- & Georg H. H. Borner
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Article
| Open Access
SYPL1 defines a vesicular pathway essential for sperm cytoplasmic droplet formation and male fertility
The cytoplasmic droplet is an elusive structure of mammalian sperm. Here, the authors uncover a key gene that defines a vesicular pathway essential for cytoplasmic droplet formation and male fertility.
- Jiali Liu
- , Louis Hermo
- & Chen Chen
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Article
| Open Access
Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired
Mitochondrial quality control is critical for cellular homeostasis and survival. Here, the authors identify that defective mitochondria can be eliminated via secretion in large extracellular vesicles when internal lysosomal degradation is compromised.
- Wenjing Liang
- , Shakti Sagar
- & Åsa B. Gustafsson
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Article
| Open Access
Self-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 Access
Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers
High neuronal proteostress can trigger the production of aggregate-filled exophers in C. elegans. Here authors show that such extrusion relies on aggregate-associated intermediate filaments and adaptors.
- Meghan Lee Arnold
- , Jason Cooper
- & Monica Driscoll
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Article
| Open Access
A signal peptide peptidase is required for ER-symbiosome proximal association and protein secretion
During nitrogen fixing symbiosis, rhizobia enter legume nodule cells to form the symbiosome. Here the authors report that a nodule-specific signal peptide peptidase is essential for the molecular communication between host cells and the symbiont.
- Jian Yang
- , Niu Zhai
- & Huairong Pan
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Article
| Open Access
RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes
RUFY proteins are known to regulate autophagy, cytoskeletal dynamics, migration and endosomal trafficking. Here, Char et al. show that iRUFY3 plays a role in perinuclear positioning, phagocyte migration and antigen presentation during Salmonella infection.
- Rémy Char
- , Zhuangzhuang Liu
- & Philippe Pierre
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Article
| Open Access
Hypoxia-reprogramed megamitochondrion contacts and engulfs lysosome to mediate mitochondrial self-digestion
Several organelle membranes make contact in the cell, with many contacts being spatially segregated sites dedicated to specific functions. Here, Hao et al. show that hypoxia increases mitochondria-lysosome contacts, leading to engulfment and degradation of the mitochondria.
- Tianshu Hao
- , Jianglong Yu
- & Zhiyin Song
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Article
| Open Access
Loss of the batten disease protein CLN3 leads to mis-trafficking of M6PR and defective autophagic-lysosomal reformation
CLN3 mutations cause Batten disease, a devastating neurodegenerative lysosomal storage disease. Here, the authors discovered that CLN3 plays a crucial role in both trafficking of lysosomal proteins and autophagic lysosomal reformation.
- Alessia Calcagni’
- , Leopoldo Staiano
- & Andrea Ballabio
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Article
| Open Access
Tetraspanin-8 sequesters syntaxin-2 to control biphasic release propensity of mucin granules
The mechanisms regulating granule secretion are not fully understood. Here the authors show that tetraspanin-8 sequesters syntaxin-2 at the cell surface, limiting the syntaxin available for fusion and the quantities of mucin secreted. This mechanism may also apply to insulin release
- José Wojnacki
- , Agustin Leonardo Lujan
- & Vivek Malhotra
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Article
| Open Access
Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health
Daly, Danson and colleagues employ a multi-omic approach in neuroglioma cells to characterise endolysosomal dysfunction caused by perturbation of the evolutionarily conserved Retromer complex, highlighting Retromer’s neuroprotective function.
- James L. Daly
- , Chris M. Danson
- & Peter J. Cullen
Tracing genetic diversity captures the molecular basis of misfolding disease