Membrane trafficking

Article | 27 March 2024

The HEAT repeat protein HPO-27 is a lysosome fission factor

The conserved HEAT repeat protein HPO-27 is identified as a lysosome scission factor in Caenorhabditis elegans, and the human homologue MROH1 also serves the same function to maintain lysosomal homeostasis.

Letao Li
, Xilu Liu
& Xiaochen Wang

Article
24 January 2024 | Open Access

Motion of VAPB molecules reveals ER–mitochondria contact site subdomains

High-speed molecular tracking is integrated with three-dimensional electron microscopy to map the diffusion distribution and ultrastructure of endoplasmic reticulum-mitochondria contact sites, revealing the ability of high-speed single-molecule imaging to map contact site interface structures and corresponding diffusion landscapes.

Christopher J. Obara
, Jonathon Nixon-Abell
& Jennifer Lippincott-Schwartz

Article
20 December 2023 | Open Access

Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish

In zebrafish embryos, active complexes of Wnt5b and its membrane-bound receptor Ror2 are transported between cells via cellular protrusions called cytonemes to initiate paracrine Wnt5b signalling in cells that do not endogenously express the receptor.

Chengting Zhang
, Lucy Brunt
& Steffen Scholpp

Article
19 October 2022 | Open Access

Clathrin-associated AP-1 controls termination of STING signalling

The adaptor protein AP-1 controls the shutdown of STING signalling through a mechanism in which AP-1 recognizes a dileucine motif in phosphorylated STING, which leads to targeted transport of STING to the endolysosomal system for degradation.

Ying Liu
, Pengbiao Xu
& Andrea Ablasser

Article | 07 September 2022

A phosphoinositide signalling pathway mediates rapid lysosomal repair

Lysosomal membrane damage triggers a lipid signalling pathway that repairs lysosomes via lipid transport at newly established endoplasmic reticulum–lysosomal membrane contact sites.

Jay Xiaojun Tan
& Toren Finkel

Article
17 August 2022 | Open Access

Endocytosis in the axon initial segment maintains neuronal polarity

Endocytosis and degradation of plasma membrane proteins in the axon initial segment, together with the diffusion-barrier mechanism, maintain a polarized distribution of plasma membrane proteins in Caenorhabditis elegans, mouse, rat and human neurons.

Kelsie Eichel
, Takeshi Uenaka
& Kang Shen

Article | 18 May 2022

Intracellular lipid surveillance by small G protein geranylgeranylation

In Caenorhabditis elegans, geranylgeranyl conjugation to RAB-11.1 acts as a lipid sensor to regulate nutrient uptake and lipid metabolism in response to metabolic demand.

Abigail Watterson
, Lexus Tatge
& Peter M. Douglas

Article | 12 May 2022

The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle

The non-structural protein NSP6 in SARS-CoV-2 has a key role in viral replication by zippering the endoplasmic reticulum membrane to establish connectors between the double-membrane vesicles of the viral replication organelle and the endoplasmic reticulum.

Simona Ricciardi
, Andrea Maria Guarino
& Maria Antonietta De Matteis

Article
23 March 2022 | Open Access

Inhibition of calcium-triggered secretion by hydrocarbon-stapled peptides

Peptides that disrupt Ca²⁺-triggered membrane fusion may enable the therapeutic modulation of mucin secretory pathways.

Ying Lai
, Giorgio Fois
& Axel T. Brunger

Article | 11 December 2019

Plasma membrane V-ATPase controls oncogenic RAS-induced macropinocytosis

A whole-genome short interfering RNA screen identified vacuolar ATPase as a regulator of macropinocytosis induced by oncogenic RAS, a key determinant of tumour cell growth under nutrient-limiting conditions.

Craig Ramirez
, Andrew D. Hauser
& Dafna Bar-Sagi

Letter | 17 September 2018

Structure of the membrane-assembled retromer coat determined by cryo-electron tomography

The retromer complex (the vacuolar protein sorting heterotrimer Vps26–Vps29–Vps35) has been resolved in association with membranes and the sorting nexin protein Vps5 using cryo-electron tomography.

Oleksiy Kovtun
, Natalya Leneva
& Brett M. Collins

Letter | 12 September 2018

GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis

During starvation, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) targets GTPase-activating proteins to inhibit multiple intracellular transport pathways, thereby promoting energy homeostasis.

Jia-Shu Yang
, Jia-Wei Hsu
& Victor W. Hsu

Letter | 01 August 2018

Cryo-EM of the dynamin polymer assembled on lipid membrane

A cryo-electron microscopy structure of human dynamin-1 demonstrates conformational changes and sheds light on the fission of membranes during endocytosis.

Leopold Kong
, Kem A. Sochacki
& Jenny E. Hinshaw

Article | 02 May 2018

Catalytic activation of β-arrestin by GPCRs

Transient engagement of the G protein-coupled receptor core can act as a catalyst to activate cellular β-arrestin function after dissociation from the receptor.

Kelsie Eichel
, Damien Jullié
& Mark von Zastrow

Letter | 13 December 2017

Dynamics of phosphoinositide conversion in clathrin-mediated endocytic traffic

‘Coincidence-detecting’ phosphoinositide sensors are used to study changes in the phosphoinositide lipid species found in membranes during the development and maturation of endocytic clathrin-coated vesicles.

Kangmin He
, Robert Marsland III
& Tom Kirchhausen

Letter | 01 November 2017

A tethering complex drives the terminal stage of SNARE-dependent membrane fusion

Tethering proteins, known to mediate initial recognition and attachment during membrane fusion, are essential for driving the transition from the hemifused state to fusion pore formation.

Massimo D’Agostino
, Herre Jelger Risselada
& Andreas Mayer

Letter | 16 August 2017

CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity

CMTM6 maintains PD-L1 at the plasma membrane by inhibiting its lysosome-mediated degradation and promoting its recycling.

Marian L. Burr
, Christina E. Sparbier
& Mark A. Dawson

Letter | 11 January 2017

PLA2G16 represents a switch between entry and clearance of Picornaviridae

The phospholipase PLA2G16 is required for the entry of picornaviruses, and in its absence, virus infection is prevented by a galectin-8-mediated process.

Jacqueline Staring
, Eleonore von Castelmur
& Thijn R. Brummelkamp

Letter | 31 October 2016

Multiple dynamin family members collaborate to drive mitochondrial division

The classical dynamin Dyn2 is required for mitochondrial division.

Jason E. Lee
, Laura M. Westrate
& Gia K. Voeltz

Letter | 24 August 2016

An endosomal tether undergoes an entropic collapse to bring vesicles together

A new endosomal tethering mechanism involving a mechanochemical cycle of the dimeric coiled-coil protein EEA1 regulated by Rab5:GTP binding and GTP hydrolysis.

David H. Murray
, Marcus Jahnel
& Marino Zerial

Letter | 27 July 2016

A trans-synaptic nanocolumn aligns neurotransmitter release to receptors

Synaptic vesicle fusion, as evoked by action potentials, is confined to presynaptic protein nanoclusters, which are closely aligned with concentrated postsynaptic receptors and their scaffolding proteins—an organization termed a ‘nanocolumn’.

Ai-Hui Tang
, Haiwen Chen
& Thomas A. Blanpied

Letter | 13 January 2016

A phosphoinositide conversion mechanism for exit from endosomes

A mechanism for phosphoinositide conversion at endosomes to enable exit from the endosomal system, suggesting that defective phosphoinositide conversion at endosomes underlies X-linked centronuclear myopathy.

Katharina Ketel
, Michael Krauss
& Volker Haucke

Letter | 10 December 2015

Polarized endosome dynamics by spindle asymmetry during asymmetric cell division

Central spindle asymmetry, generated by the kinesin Klp10A and its antagonist Patronin, polarizes endosome motility and provides a mechanism for the asymmetric segregation of signalling endosomes observed in a variety of asymmetrically dividing cell types.

Emmanuel Derivery
, Carole Seum
& Marcos Gonzalez-Gaitan

Letter | 24 August 2015

Crystal structure of the dynamin tetramer

The crystal structure of the large GTPase dynamin tetramer is presented, suggesting a mechanism by which oligomerization of dynamin is regulated, and revealing how mutations that interfere with tetramer formation and autoinhibition are of relevance to understanding the congenital muscle disorders Charcot–Marie–Tooth neuropathy and centronuclear myopathy.

Thomas F. Reubold
, Katja Faelber
& Susanne Eschenburg

Letter | 29 June 2015

A hemi-fission intermediate links two mechanistically distinct stages of membrane fission

The GTPase dynamin provides the driving force for fission of membrane-bound vesicular structures; here, it is shown that dynamin-driven membrane fission proceeds in two mechanistically distinct stages that are separated by a metastable hemi-fission intermediate that requires GTP hydrolysis for progression to full fission.

Juha-Pekka Mattila
, Anna V. Shnyrova
& Vadim A. Frolov

Letter | 03 June 2015

ESCRT-III controls nuclear envelope reformation

The ESCRT-III complex is implicated in the reformation of the nuclear envelope; the CHMP2A component of ESCRT-III is directed to the forming nuclear envelope through classical ESCRT-assembly mechanisms, with the help of the p97 complex component UFD1, and provides an activity essential for nuclear envelope reformation.

Yolanda Olmos
, Lorna Hodgson
& Jeremy G. Carlton

Letter | 03 June 2015

Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing

ESCRT-III, a protein complex best known for membrane constriction and sealing during various cellular processes, mediates reassembly of the nuclear envelope during late anaphase.

Marina Vietri
, Kay O. Schink
& Harald Stenmark

Letter | 06 May 2015

Coordinated regulation of bidirectional COPI transport at the Golgi by CDC42

The COPI complex, which has a role in retrograde transport through the Golgi, is shown to also mediate anterograde tubular transport through the Golgi; in response to external stimuli, the small GTPase CDC42 acts as an essential modulator of bidirectional Golgi transport, and promotes the sorting of cargoes destined for anterograde transport into the tubules at the expense of those targeted for retrograde transport.

Seung-Yeol Park
, Jia-Shu Yang
& Victor W. Hsu

Letter | 09 April 2015

Repeated ER–endosome contacts promote endosome translocation and neurite outgrowth

Repeated contacts between the endoplasmic reticulum (ER) and a subset of endosomes called late endosomes (LEs) is shown to promote microtubule-dependent translocation of LEs to the cell periphery and their subsequent fusion with the plasma membrane to induce outgrowth of neuronal protrusions.

Camilla Raiborg
, Eva M. Wenzel
& Harald Stenmark

Letter | 09 February 2015

ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes

The essential autophagy mediator ATG14 promotes vesicle fusion by forming homo-oligomers, which bind to a component of the SNARE membrane fusion complex and stabilize this complex on autophagosomes.

Jiajie Diao
, Rong Liu
& Qing Zhong

Article | 12 January 2015

Mechanistic insights into the recycling machine of the SNARE complex

Using single-particle electron cryomicroscopy, several structures are reported which illuminate the mechanisms of action of the ATPase NSF that disassembles the SNARE complex into individual protein components.

Minglei Zhao
, Shenping Wu
& Axel T. Brunger

Article | 17 December 2014

Endophilin marks and controls a clathrin-independent endocytic pathway

This study describes a fast, clathrin-independent endocytic pathway mediated by endophilin, dynamin and actin; the pathway is activated by ligand binding to a variety of cargo receptors, and endophilin-mediated endocytosis occurs primarily at the leading edges of cells where lamellipodin and the lipid PtdIns(3,4)P₂ ensure endophilin targeting.

Emmanuel Boucrot
, Antonio P. A. Ferreira
& Harvey T. McMahon

Letter | 17 December 2014

Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis

Endophilin-A2 (endoA2) is shown to mediate clathrin-independent endocytosis of Shiga and cholera toxins, and to function in parallel with dynamin and actin in the pulling-force-driven scission of Shiga-toxin-induced tubular structures.

Henri-François Renard
, Mijo Simunovic
& Ludger Johannes

Letter | 03 December 2014

The ESCRT machinery regulates the secretion and long-range activity of Hedgehog

A new role for the endosomal sorting complex required for transport (ESCRT) is identified in fly larvae, where it is shown to be essential for the secretion and long-range signalling of the embryonic development morphogen Hedgehog.

Tamás Matusek
, Franz Wendler
& Pascal P. Thérond

Article | 08 October 2014

Clathrin regenerates synaptic vesicles from endosomes

Ultrastructural analysis of synaptic vesicle recycling reveals that clathrin is not required for the initial rapid step of vesicle recycling by ultrafast endocytosis at the plasma membrane and instead clathrin acts later at an endosome to regenerate synaptic vesicles; however, when ultrafast endocytosis does not occur (for example, in experiments at room temperature rather than physiological temperature), clathrin-mediated endocytosis does happen at the plasma membrane.

Shigeki Watanabe
, Thorsten Trimbuch
& Erik M. Jorgensen

Letter | 18 May 2014

Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer

Several proteins localized at membrane contact sites contain an SMP domain, which has been proposed to act as a lipid-binding module; here, the crystal structure of a fragment of the extended synaptotagmin 2 protein, including its SMP, is presented, and indicates that this protein may have a direct role in lipid transport.

Curtis M. Schauder
, Xudong Wu
& Karin M. Reinisch

Article | 04 December 2013

Ultrafast endocytosis at mouse hippocampal synapses

Sustained neurotransmission requires recycling of synaptic vesicles, but the proposed mechanisms have been controversial; here a ‘flash-and-freeze’ method for electron microscopy reveals a new ultrafast form of endocytosis that is actin- and dynamin-dependent and occurs within 100 milliseconds of stimulation.

Shigeki Watanabe
, Benjamin R. Rost
& Erik M. Jorgensen

Letter | 04 August 2013

Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi

Glucosylceramide (GlcCer), a common precursor of different glycosphingolipids, is shown to be channelled to two distinct pathways in the Golgi; non-vesicular transport from the cis- to trans-Golgi network results in the synthesis of the globo series of glycosphingolipids, whereas vesicular transport is the main source of GlcCer for ganglioside synthesis in the Golgi cisternae.

Giovanni D’Angelo
, Takefumi Uemura
& Maria Antonietta De Matteis

Letter | 03 July 2013

Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate

Phosphoinositides are important regulators of intracellular membrane traffic, and although the role of PI(4,5)P₂ has been well characterised, the function of PI(3,4)P₂ remains unclear; here the formation of PI(3,4)P₂ by the class II phosphatidylinositol-3-kinase C2α enzyme is shown to control clathrin-mediated endocytosis.

York Posor
, Marielle Eichhorn-Gruenig
& Volker Haucke

Letter | 27 March 2013

Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ

An irreversible mechanism of protein demyristoylation catalysed by invasion plasmid antigen J (IpaJ), a Shigella flexneri type III effector protein with cysteine protease activity, is described.

Nikolay Burnaevskiy
, Thomas G. Fox
& Neal M. Alto

Letter | 12 December 2012

Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis

Structural and functional analysis of the centralspindlin complex shows that it connects the mitotic spindle to the plasma membrane during cytokinesis through interactions of the C1 domain of centralspindlin’s MgcRacGAP subunit with phosphoinositide lipids.

Sergey Lekomtsev
, Kuan-Chung Su
& Mark Petronczki

Review Article | 10 October 2012

Molecular machines governing exocytosis of synaptic vesicles

A brief survey of the molecular mechanisms that give the vesicle cycle in intact synapses its efficiency.

Reinhard Jahn
& Dirk Fasshauer

Letter | 15 August 2012

Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

In vivo and in vitro studies show that the stem-cell E3 ubiquitin ligases RNF43 and ZNRF3 act as tumour suppressors in colorectal cancer models, and are involved in the negative regulation of the cancer-associated Wnt signalling pathway through limiting the cell-surface expression of Wnt receptors.

Bon-Kyoung Koo
, Maureen Spit
& Hans Clevers

Letter | 28 March 2012

Crystal structure of a membrane-embedded H⁺-translocating pyrophosphatase

A model for the coupling of proton pumping and pyrophosphatase hydrolysis is proposed.

Shih-Ming Lin
, Jia-Yin Tsai
& Yuh-Ju Sun

News & Views | 22 February 2012

Collagen secretion explained

Cells package proteins into vesicles for secretion to the extracellular milieu. A study has now identified an enzyme that modifies the packaging machinery to encapsulate unusually large proteins, such as collagen. See Article p.495

David J. Stephens

Letter | 15 January 2012

Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion

Galectin 8, a cytosolic lectin, is shown to function as a danger receptor that detects damaged vesicles and protects cells from bacterial infection by inducing autophagy.