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The efficiency of protein transfer by extracellular vesicles (EVs) remains unclear. Here, authors show that EVs from cell protrusions deliver functional Rac1 and genome-editing enzymes more efficiently than well-studied endosome-derived EVs, highlighting their potential as delivery tools.

Viruses exploit host cell machinery for replication, but their spatial cues remain elusive. Using nanochip-enabled membrane shaping, the authors discover saddle curvature association of viral proteins, revealing a new spatial regulation mechanism.

Using complementary live cell approaches together with a powerful in vitro reconstitution system, this study demonstrates the direct regulation of mitochondrial dynamics by localized changes to the lipid composition of the outer membrane.

Adipose tissue accommodates large volume changes upon expansion, but the molecular mechanisms involved are not fully understood. Here, Aboy et al. describe CAV1 Y14 phosphorylation as required for appropriate adipocyte caveolae flattening and homeostasis.

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.

While biochemical regulation initiates cell division, how mechanical forces ensure successful division remains unclear. Here, the authors develop a biomimetic model of dividing cells to characterize the cytoskeleton’s mechanical power prior to division.

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.

Yang et al. show that plasma membrane curvature promotes the site-specific formation of contacts with the endoplasmic reticulum through junctophilin-2 tethers in cardiomyocytes.

By using nuclear pore complex mimics, the authors demonstrate that the cytoplasm-facing Nup358 provides a dock for the HIV-1 capsid, and the nucleoplasm-facing Nup153 positions the capsid for NPC entry. Nup358 and Nup153 thus create an affinity gradient which regulates capsid penetration, whereas Nup62 constitutes a final NPC gatekeeper against HIV-1 capsid entry.

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.

Using cryo-electron tomography, Lopez-Robles, Scaramuzza, Astorga-Simon, Ishida et al. solve the architecture of ESCPE-1, a protein scaffold that mediates the recycling of cargo from endosome to trans-Golgi network and plasma membrane in tubular carriers.

Autophagy degrades cellular waste by engulfing it in phagophore membranes and delivering it to lysosomes for degradation. Here Mohan and colleagues identified a type of membrane coat that assembles on phagophores to guide their expansion.

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.

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.

Despite decades of research, the dynamics of clathrin-coated vesicle formation is ambiguous. Here, authors use STAR microscopy to quantify the nanoscale dynamics of vesicle formation, supporting the flexible model of clathrin-mediated endocytosis.

Lysine acetylation regulates the function of soluble proteins in vivo, yet it remains largely unexplored whether lysine acetylation regulates the function of membrane proteins. Here, the authors map lysine acetylation predominantly in membrane-interaction regions in peripheral membrane proteins and show with three candidate proteins how lysine acetylation is a regulator of membrane protein function.

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.

Liang et al. report mechanisms of migrasome biogenesis in migrating cells. They propose that sphingomyelin synthase 2 (SMS2) is required for migrasomes, first by localizing in stable puncta where they eventually form migrasome structures.

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.

BAR domain proteins are known to reshape cell membranes. Using coarse-grained molecular dynamics simulations, Simunovic and Voth demonstrate that membrane tension strongly affects the association of BAR proteins, in turn controlling their recruitment to membrane-remodelling sites.

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.

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.

Cryo-EM maps of different clathrin cage architectures and accompanying analyses lead to a consensus model of the clathrin triskelion hub, suggesting a universal assembly mode that still allows adaptation to various vesicle sizes and shapes.

Wolf et al. show that N-Ank proteins combine their curvature-sensing ankyrin repeat array and N-terminal amphipathic helix to shape membranes, and ankycorbin shapes membrane protrusions in developing neurons.

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.

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.

Sengupta et al. show that protein sorting into the membranes of budding HIV particles is dependent on lipid-based partitioning of proteins, through a mechanism initiated by HIV protein Gag oligomerization at viral assembly sites.

HER2 is frequently overexpressed in breast cancer in association with increased metastatic potential. Here, the authors show that HER2 overexpression causes deformation of cell membranes in a signalling-independent manner that contributes to the disease phenotype by disrupting epithelial features.

The E2-like enzyme Atg3 conjugates phosphatidylethanolamine (PE) to Atg8 to facilitate its membrane association and promote autophagosome maturation. Melia and colleagues report that Atg3 preferentially associates in vitro with highly curved, PE-enriched membranes, such as the isolation membrane of a nascent autophagosome, thus ensuring access to a local supply of PE.

The sequence of structural and molecular events during clathrin-mediated endocytosis is unclear. Here the authors combine correlative microscopy and simple mathematical growth laws to demonstrate that the flat patch starts to curve when around 70% of the final clathrin content is reached.

De Camilli and colleagues reveal that reducing cholesterol or sphingomyelin causes formation of tubular structures resembling early endocytic intermediates at the plasma membrane. These structures recruit sphingosine kinase 1 (SPHK1). Depleting SPHK1 inhibits endocytic recycling, revealing a link between sphingosine metabolism and endocytosis.

Membrane curvature and lipid composition direct the binding of many peripheral membrane proteins. Here, Vanni et al. use a combination of in vitroand molecular dynamics approaches to quantify how lipid-packing defects in membranes of various composition and curvature dictate the membrane adsorption of a model lipid-binding protein.

Complexin binds to synaptic vesicles and inhibits spontaneous exocytosis. Here Snead et al. show that the high curvature of the vesicle membrane is important for membrane binding, and induces a conformational change that is important for complexin’s inhibitory function.

The MICOS complex has an essential role in crista junction formation and mitochondrial inner membrane morphology. Here, the authors show that one of its components, Mic60, known to form contact sites between inner and outer membranes, also displays membrane-shaping activity.

The inverted-BAR domain protein IRSp53 associates with the inner leaflet of tubular membranes such as filopodia. Here, Prévostet al. demonstrate that the I-BAR domain of IRSp53 senses negative membrane curvature, and undergoes phase separation which may aid its clustering upon filopodia generation.

Proteins that bend membranes often contain curvature-promoting structural motifs such as wedges or crescent-shaped domains. Busch et al.report that intrinsically disordered domains can also drive membrane curvature and provide evidence that steric pressure driven by protein crowding mediates this effect.

The role of annexins in cell membrane repair is largely undefined. Here the authors use a model lipid bilayer to show that annexin A4 induces curvature at the membrane free edge and annexin A6 induces constriction force, and find that both annexins are recruited to wound edges in cells and are required for repair.

In heart muscle cells, a region of the sarcolemmal membrane periodically invaginates to form T tubules, a specialized membrane domain that contains important ion channels regulating cell contraction. Robin Shaw and his colleagues describe how a cardiac-specific splice variant of the isoform of the protein BIN1 helps make folds in T tubules, which affects the ability of ions in the extracellular space to freely diffuse and protects the heart from arrhythmia.

Elliott et al. use high-resolution imaging, microfabrication and computational analyses to show that the interplay between cell-surface curvature and activity and cortical recruitment of myosin II, control cell migration in 3D matrices.

Mi et al. show that CapZ regulates autophagosomal membrane shaping by controlling the assembly of an actin scaffold in the autophagosomal precursor.

Itoh and colleagues find that the membrane-bending protein FBP17 is released from membranes at the leading edge of migrating cells following increased tension involving a feedback loop, in which FBP17 also promotes tension through actin protrusion formation.

Many cell surface receptors are internalized by clathrin-independent endocytosis, but how clathrin-independent carriers (CLICs) are generated at the plasma membrane remained unclear. Johannes and colleagues now report that galectin-3 (Gal3) binds to glycosylated cargo proteins and glycosphingolipids. These interactions induce membrane deformation, revealing a mechanism for CLIC biogenesis.

Coat protein complex II (COPII) subunits assemble to form membrane transport carriers at ER exit sites, thereby concentrating secretory cargoes and facilitating their transport to the Golgi. This Review discusses the mechanisms of coat assembly and disassembly, and cargo recognition by COPII carriers.

This protocol describes the design and fabrication of nanoscale structures for studying intracellular responses to membrane curvature, which are visualized by fluorescence imaging; FIB–SEM is used to characterize the nanostructure–cell interface.

N-BAR-domain-containing proteins regulate membrane dynamics, as they stabilize curved membrane topologies, but whether they primarily sense or generate curvature has remained unclear. Galic, Meyer and colleagues now report that N-BAR proteins accumulate at highly curved membrane areas.

Membrane deformation is necessary to generate endocytic vesicles, but the molecular mechanisms proposed to drive membrane bending are controversial. Stachowiak and Schmid et al. report that crowding of proteins at the membrane is sufficient to induce curvature in vitro.

Khan et al. perform AAV9-cBIN1 gene therapy in a canine model of acquired chronic ischemic cardiomyopathy. They show AAV9-cBIN1 therapy mitigates disease progression and can reverse heart failure in this model.

Endosomal sorting complexes required for transport (ESCRTs) are key membrane remodellers, which drive the budding, scission and sealing of various cellular membranes. Accordingly, ongoing research focuses on how ESCRTs mediate a wide-range of cellular processes, including cytokinesis, endosome maturation, autophagy, membrane repair and viral replication.

TMEM16E is a calcium-dependent scramblase that mediates ion transport and lipid translocation, contributing to membrane protection. This study shows TMEM16E promotes macropinocytosis, crucial for maintaining plasma membrane integrity.

Multiple processes in the cell require curved membranes. Stachowiak, Brodsky and Miller discuss how lipids and vesicle cargo proteins represent energy barriers to membrane bending, and how different mechanisms may operate to overcome these barriers as drivers of membrane curvature.