Featured
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| Open AccessRUFY3 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 AccessHypoxia-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 AccessLoss 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 AccessTetraspanin-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 AccessMulti-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
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Article
| Open AccessPhospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism
Phospholipase D3 polymorphisms are linked to late-onset Alzheimer’s disease but the mechanisms are not understood. Van Acker and colleagues show that Phospholipase D3 processes mitochondrial DNA in lysosomes to maintain lysosomal homeostasis and proper degradation of the amyloid precursor protein.
- Zoë P. Van Acker
- , Anika Perdok
- & Wim Annaert
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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 AccessZinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface
Zinc is vital to protein quality control in the early secretory pathway. Here, authors demonstrate distinct roles of the Golgi-resident zinc transporters for the maintenance of zinc homeostasis and the regulation of a zinc-dependent chaperone, ERp44.
- Yuta Amagai
- , Momo Yamada
- & Kenji Inaba
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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 AccessSynDLP is a dynamin-like protein of Synechocystis sp. PCC 6803 with eukaryotic features
In eukaryotes, dynamins and dynamin-like proteins (DLPs) are involved in various membrane remodeling processes. Here, the authors present the structure and functional characterization of a DLP of the cyanobacterium Synechocystis sp. PCC 6803.
- Lucas Gewehr
- , Benedikt Junglas
- & Dirk Schneider
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Article
| Open AccessASPSCR1::TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma
The mechanisms of angiogenesis in alveolar soft part sarcoma (ASPS) remain to be explored. Here, the authors highlight the role of the ASPSCR1::TFE3 fusion in regulating super-enhancer activity during the angiogenic process in ASPS.
- Miwa Tanaka
- , Surachada Chuaychob
- & Takuro Nakamura
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Article
| Open AccessThe K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper
In contrast to the current model based on fast recycling of the K/HDEL receptor (ERD2) between the ER and the Golgi apparatus, here authors show evidence that ERD2 is specifically retained in the Golgi apparatus and evades joining its ligands en route to the ER.
- Jonas C. Alvim
- , Robert M. Bolt
- & Jurgen Denecke
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Article
| Open AccessStructural basis for TRIM72 oligomerization during membrane damage repair
TRIM72 oligomerization via intermolecular disulfide bonds is important for cells to repair damaged membranes. Here, authors report the crystal structure of TRIM72 dimer and show that TRIM72 B-box dimerization facilitates TRIM72 oligomerization.
- Yuemin Ma
- , Lei Ding
- & Chun Zhou
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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 AccessOrthodenticle homeobox 2 is transported to lysosomes by nuclear budding vesicles
Many homeodomain transcription factors are secreted and move to neighboring cells. Here, orthodenticle homeobox 2 is shown to be exported from the nucleus in a nuclear membrane, which buds off to then be degraded or secreted.
- Jun Woo Park
- , Eun Jung Lee
- & Jin Woo Kim
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Article
| Open AccessTetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes
Migrasomes are signaling organelles that form in retraction fibers of migrating cells. Here authors show that migrasomes form by a two-stage process: an initial local membrane swelling matures and is stabilized by recruited tetraspanin proteins.
- Raviv Dharan
- , Yuwei Huang
- & Raya Sorkin
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Article
| Open AccessSugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts
Despite the importance of osteoclast secretory lysosomes in bone digestion, the proteins that regulate them remain ill defined. Here, the authors identify Slc37a2 as a secretory lysosome sugar transporter that is required for maintenance of skeletal bone mass.
- Pei Ying Ng
- , Amy B. P. Ribet
- & Nathan J. Pavlos
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| Open AccessSpatial proteomics reveals secretory pathway disturbances caused by neuropathy-associated TECPR2
Disease-associated mutations in the protein TECPR2 have so far been mainly studied with respect to autophagy. Using complementary proteomics approaches, the authors identify trafficking and sorting defects along the secretory pathway upon TECPR2 deficiency and provide evidence that TECPR2 associates with the ER-Golgi interface.
- Karsten Nalbach
- , Martina Schifferer
- & Christian Behrends
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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 AccessThe p97-UBXD8 complex regulates ER-Mitochondria contact sites by altering membrane lipid saturation and composition
Inter-organellar contacts are hubs for several critical cellular processes, such as lipid synthesis. Here Ganji et al. show that the p97-UBXD8 complex modulates contacts by regulating membrane lipid composition and saturation.
- Rakesh Ganji
- , Joao A. Paulo
- & Malavika Raman
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Article
| Open AccessESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling
STING is an intracellular sensor of pathogen- or host-derived DNA. In this study, the authors identify an ESCRT complex that regulates STING degradation, thus acting as a homeostatic regulator of STING signalling and type-I interferon responses.
- Matteo Gentili
- , Bingxu Liu
- & Nir Hacohen
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Article
| Open AccessExocytosis of the silicified cell wall of diatoms involves extensive membrane disintegration
Exocytosis is a fundamental cellular process. Here, the authors report an unusual exocytosis mechanism in the silicified cell wall of diatoms, in which membrane patches are discarded.
- Diede de Haan
- , Lior Aram
- & Assaf Gal
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Article
| Open AccessGlycolysis regulates KRAS plasma membrane localization and function through defined glycosphingolipids
KRAS is a small GTPase that regulates cell proliferation. Here, the authors show that a subset of cell surface glycosphingolipids regulate KRAS plasma membrane localization by modulating inner leaflet lipid composition, uncovering a requirement for KRAS oncogenesis that may have therapeutic potential.
- Junchen Liu
- , Ransome van der Hoeven
- & John F. Hancock
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Article
| Open AccessBroad misappropriation of developmental splicing profile by cancer in multiple organs
The molecular mechanisms underlying the overlap between oncogenic and embryonic development remain to be explored. Here, the authors use temporal transcriptomic data during development in multiple human organs and suggest the involvement of alternative splicing events, splicing factors, and transcription factors.
- Arashdeep Singh
- , Arati Rajeevan
- & Sridhar Hannenhalli
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Article
| Open AccessCryo-electron tomography reveals structural insights into the membrane remodeling mode of dynamin-like EHD filaments
Eps15-homology domain containing proteins comprise a family of dynamin-related ATPases. Here, Melo et al. use cryo-electron tomography to determine the membrane-bound EHD4 structure, therefore clarifying the membrane binding and oligomerization mode.
- Arthur A. Melo
- , Thiemo Sprink
- & Oliver Daumke
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Comment
| Open AccessGolgipathies reveal the critical role of the sorting machinery in brain and skeletal development
Association genetic studies and genome-scale CRISPR screens have recently identified ARF3 and TMEM251/LYSET/GCAF as Golgi-resident factors essential to brain and skeletal development. Here we discuss how even though the consequences of mutations in these genes affect endosomal and lysosomal compartments, the problem originates in the Golgi complex and may involve either the identity of the carrier vesicles or that of cargo molecules.
- Vincent El Ghouzzi
- & Gaelle Boncompain
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Article
| Open AccessLysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism
Extensive lysosomal damage can result in cell death but how limited protease leakage affects cytoplasmic organelles in viable cells is not well understood. Here the authors show that limited lysosomal damage leads to changes in the mitochondrial proteome and the modulation of macrophage immunometabolism.
- Claudio Bussi
- , Tiaan Heunis
- & Maximiliano G. Gutierrez
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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 AccessA multivesicular body-like organelle mediates stimulus-regulated trafficking of olfactory ciliary transduction proteins
Odor stimuli are transduced in cilia of olfactory sensory neurons. Here the authors identify an odor stimulus-regulated organelle that specifically stores and releases transduction proteins in the dendrite.
- Devendra Kumar Maurya
- , Anna Berghard
- & Staffan Bohm
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Article
| Open AccessDifferential impact of ubiquitous and muscle dynamin 2 isoforms in muscle physiology and centronuclear myopathy
Dynamin 2 is a large GTPase linked to several human diseases. Here, Gómez-Oca et al. investigate the functions of muscle dynamin 2 isoforms and provide insights into their differential implication in centronuclear myopathy pathogenesis and treatment.
- Raquel Gómez-Oca
- , Evelina Edelweiss
- & Jocelyn Laporte
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Article
| Open AccessA conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience
Environmental temperature changes can alter cell membrane lipid composition but the mechanisms underlying this conserved mechanism are unclear. Here, the authors identify the megaprotein LPD-3 in C. elegans as critical for normal phospholipid distribution and cold resilience.
- Changnan Wang
- , Bingying Wang
- & Dengke K. Ma
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Article
| Open AccessMitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA
Mitochondrial quality control mechanisms prevent damage accumulation, including in mitochondrial DNA (mtDNA). Here, Sen et al. show that altered mtDNA elicits local rearrangements in mitochondrial membrane potential and cristae structure, with mtDNA eliminated through VPS35 endosomes.
- Ayesha Sen
- , Sebastian Kallabis
- & David Pla-Martín
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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 AccessPlasma membrane flipping of Syntaxin-2 regulates its inhibitory action on insulin granule exocytosis
Kang and colleagues find that plasma membrane flipping of Syntaxin-2 from inside (inhibitory) to outside (relief of inhibition) of pancreatic β-cells helps fine-tune insulin secretion. Increasing this flipping efficiency can alleviate the impaired insulin secretion in diabetes.
- Fei Kang
- , Li Xie
- & Herbert Y. Gaisano
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Article
| Open AccessGlutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling
The PI3K/AKT signaling pathway is carefully regulated in specific cellular compartments. Lee and colleagues show that the housekeeping gene glutamyl-prolyl-tRNA synthetase 1 coordinates early endosome-specific AKT signaling necessary for inflammation resolution.
- Eun-Young Lee
- , Su-Man Kim
- & Myung Hee Kim
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Article
| Open AccessThe cholesterol transport protein GRAMD1C regulates autophagy initiation and mitochondrial bioenergetics
The functions of specific lipids in autophagosome biogenesis are not entirely clear. Here, the authors show that the ER protein GRAMD1C, a cholesterol transport protein, suppresses autophagy initiation and has roles in mitochondrial cholesterol homeostasis and respiration.
- Matthew Yoke Wui Ng
- , Chara Charsou
- & Anne Simonsen
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Article
| Open AccessWASH activation controls endosomal recycling and EGFR and Hippo signaling during tumor-suppressive cell competition
Polarity-deficient epithelial cells are eliminated through Sas-Ptp10D-mediated suppression of EGFR signalling during cell competition. Here the authors show the constitutively active, phosphomimetic WASH can activate both EGFR and Hippo signalling and thereby, induces the overgrowth of these polarity-deficient cells in Drosophila and in proliferating epithelial cells, WASH activation differentially affects the separate recycling routes of EGFR and its inhibitor Ptp10D.
- Dan Liu
- , Vasilios Tsarouhas
- & Christos Samakovlis
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Article
| Open AccessThe unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans
Endoplasmic reticulum stress activates the unfolded protein response (UPR). The authors show that glucose extends the lifespan of aged animals by activating the otherwise quiescent UPR while causing a UPR-dependent reduced longevity in young animals
- Caroline Beaudoin-Chabot
- , Lei Wang
- & Guillaume Thibault
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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 AccessResolving subcellular pH with a quantitative fluorescent lifetime biosensor
Measuring sub-cellular pH with high accuracy and spatiotemporal resolution remains challenging. Here, Johnston and co-workers develop a pH biosensor that combines the pH dependant fluorescent lifetime of mApple with deep learning to accurately determine sub-cellular pH in individual vesicles.
- Joshua J. Rennick
- , Cameron J. Nowell
- & Angus P. R. Johnston
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Article
| Open AccessTargeting EGFR-dependent tumors by disrupting an ARF6-mediated sorting system
EGFR is aberrantly activated in many cancer types. Here the authors show that small GTPase ARF6 mediates the trafficking of palmitoylated EGFR from Golgi to plasma membrane and the blockade of this sorting system inhibits the growth of EGFR overexpression tumours.
- Huiling Guo
- , Juan Wang
- & Tong-Jin Zhao
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Article
| Open AccessThe lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase
In this work, the authors report an ATP-dependent phosphatidylserine floppase activity for the lysosomal ATP-binding cassette transporter TAPL. In addition, they report the cryo-EM structures of mouse TAPL complexed with (i) phospholipid, (ii) cholesteryl hemisuccinate (CHS) and 9-mer peptide, and (iii) ADP·BeF3. Together, their results suggest that TAPL uses different mechanisms to function as a peptide translocase and a phosphatidylserine floppase.
- Jun Gyou Park
- , Songwon Kim
- & Mi Sun Jin
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Article
| Open AccessLocation bias contributes to functionally selective responses of biased CXCR3 agonists
Subcellular signaling is critical to generating cellular responses that modulate inflammatory pathways at the chemokine receptor CXCR3. Eiger et al. determine that agonist-biased CXCR3 signaling at endosomes differs from that at the plasma membrane, proposing location bias as an important phenomenon in signal transduction.
- Dylan Scott Eiger
- , Noelia Boldizsar
- & Sudarshan Rajagopal
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Article
| Open Accessβ-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells
Here the authors present improved intramolecular sensors for β-arrestin2 and 1, which enable assessment of conformational changes of both isoforms in living cells. These reveal that the same GPCR induces differential conformational rearrangements that determine the functional diversity between the two β-arrestins.
- Raphael S. Haider
- , Edda S. F. Matthees
- & Carsten Hoffmann
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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 AccessDifferential dysregulation of granule subsets in WASH-deficient neutrophil leukocytes resulting in inflammation
Responsive exocytosis in neutrophil leukocytes involves actin depolymerisation-dependent sequential release of gelatinase granules, then strongly pro-inflammatory azurophilic granules. Here authors show that the actin nucleator protein WASH facilitates the initial step of innate immune activation by gelatinase granules while inhibiting release of pro-inflammatory granules.
- Jennifer L. Johnson
- , Elsa Meneses-Salas
- & Sergio D. Catz
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Article
| Open AccessGCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway
Lysosomal biogenesis errors often result in diseases including mucolipidosis. Here Zhang and Yang et al. identify TMEM251/GCAF as a mannose-6-phosphate modification regulator that is necessary for correct lysosomal targeting, and classify Mucolipidosis Type V as resulting from GCAF mutations.
- Weichao Zhang
- , Xi Yang
- & Ming Li
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Comment
| Open AccessBidirectional lysosome transport: a balancing act between ARL8 effectors
Most organelles move bidirectionally on microtubule tracks, yet how this opposing movement is regulated by kinesin and dynein remains unclear. Recent work found that ARL8, a known anterograde adaptor linking the lysosome to kinesin, also links lysosomes to the retrograde motor dynein, providing key insight into bidirectional organelle movement in cells.
- Agnieszka A. Kendrick
- & Jenna R. Christensen
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Article
| Open AccessmTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1
mTORC1 is a master regulator of cell growth with well-known functions in inhibiting autophagic vesicle formation. Here, the authors show that mTORC1 also affects Golgi architecture and vesicle secretion by phosphorylating the scaffold protein SCYL1.
- Stéphanie Kaeser-Pebernard
- , Christine Vionnet
- & Jörn Dengjel