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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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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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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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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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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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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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ASPSCR1::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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Glycolysis 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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Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector
Rep15 is an effector that interacts with the GTPase Rab15. Here, the authors show that Rep15 also interacts with Rab3 paralogs and Rab34, present crystal structures of Rep15:Rab complexes and find that Rep15 depletion in glioblastoma cells decreases proliferation and mobility.
- Amrita Rai
- , Anurag K. Singh
- & Roger S. Goody
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RUFY3 and RUFY4 are ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin
Organellar transport is carefully regulated, and endolysosome localized ARL8 is important for kinesin recruitment and anterograde movement. Here, the authors show that RUFY3 and RUFY4 promote retrograde transport of endolysosomes by mediating interaction of ARL8 with dynein-dynactin.
- Tal Keren-Kaplan
- , Amra Sarić
- & Juan S. Bonifacino
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TRAPPC4 regulates the intracellular trafficking of PD-L1 and antitumor immunity
Transport protein particle (TRAPP) is a multimeric protein complex regulating membrane trafficking pathways. Here the authors show that TRAPPC4, a core subunit of TRAPP complex, is required for RAB11-mediated recycling of PD-L1, affecting T-cell-mediated anti-tumor immune responses.
- Yimeng Ren
- , Yun Qian
- & Jing-Yuan Fang
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TMEM16F and dynamins control expansive plasma membrane reservoirs
Cells locally expand and retract their surface in response to environmental factors such as changes in membrane tension. Here the authors show the membrane adapter, dynamin2, locally constricts surface membrane to form an isolated but contiguous membrane reservoir that can open upon phospholipid scrambling via TMEM16F.
- Christine Deisl
- , Donald W. Hilgemann
- & Michael Fine
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A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export
Lysosomes play an important role in cellular LDL-cholesterol uptake. Here, the authors perform a genome-wide genetic screen for cholesterol regulators and identify C18orf8 as a conserved subunit of a trimeric Rab7 GEF that controls LDL trafficking and NPC1-dependent lysosomal cholesterol export.
- Dick J. H. van den Boomen
- , Agata Sienkiewicz
- & Paul J. Lehner
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Rab35-regulated lipid turnover by myotubularins represses mTORC1 activity and controls myelin growth
Charcot-Marie-Tooth (CMT) is an inherited peripheral neuropathy. Here, the authors show that Rab35 forms a complex with genes implicated in CMT, MTMR13 and MTMR2, which regulates myelin growth by controlling mTORC1 signaling through lipid turnover.
- Linda Sawade
- , Federica Grandi
- & Volker Haucke
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Miro 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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ZFYVE21 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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Amino acids stimulate the endosome-to-Golgi trafficking through Ragulator and small GTPase Arl5
Amino acid levels are known to regulate anabolic and catabolic pathways. Here, the authors report that amino acids also affect membrane trafficking by stimulating endosome-to-Golgi retrograde trafficking and regulating cell surface localization of certain Golgi proteins through Ragulator and Arl5.
- Meng Shi
- , Bing Chen
- & Lei Lu
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Subtomogram averaging of COPII assemblies reveals how coat organization dictates membrane shape
The COPII coat assembles in two concentric layers and mediates protein export from the endoplasmic reticulum. Here the authors present the 4.9 Å resolution cryo-tomography and subtomogram averaging structure of the membrane bound COPII inner coat that was obtained by in vitro reconstitution and discuss mechanistic implications.
- Joshua Hutchings
- , Viktoriya Stancheva
- & Giulia Zanetti
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Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5
Rab11 GTPases are involved in various cellular processes but their activation by guanine nucleotide exchange factors (GEFs) is not fully understood. Here, the authors present a structural and biochemical analysis of Rab11 bound to the GEF SH3BP5, providing insights how Rab-GEF specificity is achieved.
- Meredith L. Jenkins
- , Jean Piero Margaria
- & John E. Burke
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Small GTPases and BAR domain proteins regulate branched actin polymerisation for clathrin and dynamin-independent endocytosis
Several endocytic pathways operate simultaneously at the cell surface, including the clathrin and dynamin-independent CLIC/GEEC (CG) pathway. Here the authors show that small GTPases and BAR domain proteins regulate branched actin to make clathrin and dynamin-independent endocytic vesicles.
- Mugdha Sathe
- , Gayatri Muthukrishnan
- & Satyajit Mayor
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Coupling fission and exit of RAB6 vesicles at Golgi hotspots through kinesin-myosin interactions
Actin and microtubules play important roles in Golgi structure and function but how they are connected is poorly understood. Here the authors show that KIF20A is involved in the fission process and, in association with Myosin II, serves to anchor RAB6 on Golgi/TGN membranes near microtubules nucleating sites.
- Stéphanie Miserey-Lenkei
- , Hugo Bousquet
- & Bruno Goud
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Routing of the RAB6 secretory pathway towards the lysosome related organelle of melanocytes
The anterograde movement of Golgi-derived vesicles requires the small GTPase RAB6, while its effector ELKS targets these vesicles to particular areas of the plasma membrane. Here the authors show that RAB6 and ELKS function in the biogenesis of melanosome, demonstrating that the secretory pathway can be directed towards intracellular organelles of endosomal origin.
- Anand Patwardhan
- , Sabine Bardin
- & Cédric Delevoye
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Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1–Ccz1
The Mon1-Ccz1 (MC1) complex is a Rab guanine nucleotide exchange factor (RabGEF) for Ypt7/Rab7 important for endosomal maturation. Here the authors present the biochemical and structural characterization of MC1, elucidating its catalytic mechanism and showing that MC1 represents novel class of RabGEFs.
- Stephan Kiontke
- , Lars Langemeyer
- & Daniel Kümmel
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Pre-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
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Dual 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
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miR-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
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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
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A 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
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TD-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
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RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock
Histamine causes vascular leakage by a direct and yet mechanistically poorly defined effect on endothelium. Here, the authors show that histamine elicits endothelial RhoA/Rock signaling and that inhibition of this pathway preserves the vascular barrier, thereby identifying novel pharmacological targets for histamine-mediated diseases.
- Constantinos M. Mikelis
- , May Simaan
- & J. Silvio Gutkind
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The intellectual disability protein RAB39B selectively regulates GluA2 trafficking to determine synaptic AMPAR composition
Mutations in the RAB39Bgene, which encodes a protein involved in vesicular trafficking, are associated with intellectual disability, but the impact of RAB39B loss of function on synaptic activity is not known. Here the authors show that RAB39B interacts with PICK1, and that this interaction is critical for the translocation of AMPA receptor subunits into the Golgi.
- Maria Lidia Mignogna
- , Maila Giannandrea
- & Patrizia D’Adamo
Rab30 facilitates lipid homeostasis during fasting