Featured
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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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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
| 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
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
Structural 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 Access
FERARI and cargo adaptors coordinate cargo flow through sorting endosomes
It is estimated that about 80% of endocytosed material is recycled back to the plasma membrane. Here, the authors show that kiss-and-run of Rab5 early endocytic and Rab11 recycling vesicles on sorting endosomes allow cargo flow, providing more robustness and fidelity to the sorting process.
- Jachen A. Solinger
- , Harun-Or Rashid
- & Anne Spang
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Article
| Open Access
Stomatin modulates adipogenesis through the ERK pathway and regulates fatty acid uptake and lipid droplet growth
Stomatin is a component of lipid rafts. Here, Wu et al. show that stomatin modulates the differentiation and functions of adipocytes by regulating adipogenesis signaling and fatty acid influx such that with excessive calorie intake, increased stomatin induces adiposity.
- Shao-Chin Wu
- , Yuan-Ming Lo
- & Chi-Hung Lin
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Article
| Open Access
Free energies of membrane stalk formation from a lipidomics perspective
Fusion of cellular membranes begins with the formation of a stalk. Here, the authors develop a computationally efficient method for coarse-grained simulations of stalk formation and apply this approach to comprehensively analyse how stalk formation is influenced by the membrane lipid composition.
- Chetan S. Poojari
- , Katharina C. Scherer
- & Jochen S. Hub
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Article
| Open Access
YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion
Cells in many tissues fuse into syncytia acquiring new functions. By investigating whether physical remodelling promotes differentiation, here, the authors show that plasma membrane diminution post-fusion causes transient nutrient stress that inhibits YAP1 activity and may reduce proliferation-promoting transcription.
- Daniel Feliciano
- , Carolyn M. Ott
- & Jennifer Lippincott-Schwartz
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Article
| Open Access
Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
Macrophages are critical in limiting replication of herpes simplex virus type 1 (HSV-1). Here the authors show how acid ceramidase and its enzymatic product sphingosine enable multivesicular bodies to function as an anti-viral mechanism.
- Judith Lang
- , Patrick Bohn
- & Karl S. Lang
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Article
| Open Access
Structural 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 Access
KIBRA 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 Access
The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation
Cell surface receptors are thought to be internalized via the multivesicular bodies (MVBs) in an ESCRT-dependent pathway. Here, the authors report that in yeast, a hexose transporter is internalized via an ESCRT-independent pathway into intralumenal fragments (ILF).
- Erin Kate McNally
- & Christopher Leonard Brett
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Article
| Open Access
The AFF-1 exoplasmic fusogen is required for endocytic scission and seamless tube elongation
Membrane fusion and fission events at exoplasmic membrane surfaces are not well understood. Here the authors show that the C. elegans cell–cell fusogen AFF-1 is required for endocytic scission and apically-directed membrane trafficking during the development of a unicellular tube.
- Fabien Soulavie
- , David H. Hall
- & Meera V. Sundaram
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Article
| Open Access
An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion
Mitochondrial fusion is crucial for cellular homeostasis but its regulation is still not fully understood. Here the authors report that a cross-talk between ubiquitin protease Ubp2 and ligases Mdm30 and Rsp5 modulates mitofusin Fzo1 levels and fatty acids saturation and thus mitochondrial fusion.
- Laetitia Cavellini
- , Julie Meurisse
- & Mickael M. Cohen
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Article
| Open Access
Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis
EGFR signalling has been linked to cancer development but whether it has any role in pre-metastatic niche formation is not known. Here the authors show that gastric cancer cells send EGFR through exosomes to the liver where it causes the establishment of a favourable microenvironment thus promoting metastasis.
- Haiyang Zhang
- , Ting Deng
- & Yi Ba
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Article
| Open Access
Microtubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion
During tracheal tube fusion in Drosophila, a pair of tip cells form an adherens junction and then fuse their plasma membranes. Here the authors show that a balanced pulling force mediated by myosin and microtubules, as well as localized deposition of matrix, promotes plasma membrane fusion.
- Kagayaki Kato
- , Bo Dong
- & Shigeo Hayashi
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Article
| Open Access
Real-time intermembrane force measurements and imaging of lipid domain morphology during hemifusion
During membrane fusion, lipid bilayers come into direct contact but rearrangements of lipid domains during fusion have not been thoroughly examined. Here the authors observe and correlate membrane morphology, interaction forces and domain rearrangements during hemifusion of two model membranes.
- Dong Woog Lee
- , Kai Kristiansen
- & Jacob N. Israelachvili
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IM30 triggers membrane fusion in cyanobacteria and chloroplasts
Thylakoid membranes are critical components of chloroplasts and cyanobacteria. Here, Hennig et al. demonstrate that IM30, a conserved chloroplast and cyanobacterial protein, binds to thylakoid membranes and can trigger membrane destabilization and fusion in a Mg2+dependent manner.
- Raoul Hennig
- , Jennifer Heidrich
- & Dirk Schneider
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Metabolic cross-feeding via intercellular nanotubes among bacteria
Some bacteria can form nanotubes to transfer proteins and plasmids between neighbouring cells. Here, the authors show that nanotubes can also mediate the exchange of cytoplasmic amino acids between cells of the same or different bacterial species.
- Samay Pande
- , Shraddha Shitut
- & Christian Kost
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Article
| Open Access
A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion
Synaptic vesicle fusion involves a multi-protein assembly called the SNARE complex that is tightly regulated both spatially and temporally. Here Kavanagh et al. show that after vesicle fusion and SNARE complex disassembly in the synapse, the SNARE protein syntaxin1a is sequestered in a monomeric form by munc18-1, preventing ectopic SNARE complex assembly.
- Deirdre M. Kavanagh
- , Annya M. Smyth
- & Rory R. Duncan
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Article
| Open Access
Control of membrane gaps by synaptotagmin-Ca2+ measured with a novel membrane distance ruler
Synaptotagmin-1 (syt-1) triggers fast synchronous neurotransmission mediated by fusion of synaptic vesicles with presynaptic membranes. Here Lin et al. use inter-membrane FRET combined with DNA rulers as calibration standards to quantify Ca2+-induced changes in membrane distances mediated by syt-1.
- Chao-Chen Lin
- , Jan Seikowski
- & Peter Jomo Walla
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Post-fusion structural changes and their roles in exocytosis and endocytosis of dense-core vesicles
Fusion of vesicles with the plasma membrane generates omega-shaped intermediates that are thought to either dilate until flat or less frequently, undergo pore closure. Chiang et al.reveal that in chromaffin cells, these structures do not dilate, but change in size before pore closure or shrink until undetectable.
- Hsueh-Cheng Chiang
- , Wonchul Shin
- & Ling-Gang Wu
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Dynamin−SNARE interactions control trans-SNARE formation in intracellular membrane fusion
Dynamin promotes membrane fission by constricting the neck of invaginating membranes; however, it was recently shown that dynamin also regulates membrane fusion. Here the authors show that this fusogenic activity is mediated by interaction with the Qa SNARE, thereby promoting trans-SNARE formation.
- Kannan Alpadi
- , Aditya Kulkarni
- & Christopher Peters
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α-SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro
The energy-sensing kinase AMPK is regulated by phosphorylation, however, the identity of AMPK phosphatases remains uncertain. Here the authors show that α-SNAP, a protein previously known for its role in membrane fusion, can dephosphorylate AMPK despite lacking a recognizable phosphatase domain.
- Lifu Wang
- & David L. Brautigan
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Synaptobrevin2 is the v-SNARE required for cytotoxic T-lymphocyte lytic granule fusion
Cytotoxic T lymphocytes kill target cells through the fusion of lytic granules at the immunological synapse. Using high-resolution microscopy techniques Matti et al.identify synaptobrevin2 as the vesicular SNARE protein required for this fusion reaction.
- Ulf Matti
- , Varsha Pattu
- & Jens Rettig
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Cooperation between different RNA virus genomes produces a new phenotype
RNA viruses are known to rapidly evolve new features through errors in replication and reshuffling of genomic segments. These authors report another strategy used by the measles virus to improve infectivity; the cooperation between wild-type and mutant fusion proteins in the same viral particle.
- Yuta Shirogane
- , Shumpei Watanabe
- & Yusuke Yanagi
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G-protein β2 subunit interacts with mitofusin 1 to regulate mitochondrial fusion
Little is known about the regulation of mitofusin proteins that are involved in the fusion of mitochondrial membranes. In this study, the authors report that a heterotrimeric G protein, Gβ-subunit 2, can interact with mitofusin 1, and is involved in the regulation of mitochondrial fusion.
- Juan Zhang
- , Weihua Liu
- & Quan Chen
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A single-vesicle content mixing assay for SNARE-mediated membrane fusion
SNARE protein-mediated vesicle fusion is usually monitored by indirect lipid mixing. Diaoet al. have developed a FRET-based single-vesicle content mixing assay, which elucidates fusion pore formation, and shows that the yeast SNARE complex mediates pore expansion in the absence of accessory proteins.
- Jiajie Diao
- , Zengliu Su
- & Taekjip Ha
Differential SNARE chaperoning by Munc13-1 and Munc18-1 dictates fusion pore fate at the release site