Endophilin A3-mediated clathrin-independent endocytosis (EndoA3-mediated CIE) contributes to the internalization of immunoglobulin-like proteins, including key immune synapse components. Here, we identify ICAM1 as a novel EndoA3-dependent cargo, alongside ALCAM. We demonstrate that both proteins subsequently follow retromer-dependent retrograde transport to the trans-Golgi network (TGN) in cancer cells. From there, we propose that they undergo polarized redistribution to the plasma membrane, where they contribute to immune synapse formation between cancer cells and cytotoxic CD8 T cells. Disruption of EndoA3 or retromer components significantly affects the response of autologous cytotoxic CD8 T cells, as evidenced by reduced cytokine production and secretion, but increased lytic activity, while proliferation and later activation marker expression remain intact. This is accompanied by diminished ICAM1 density at the immune synapse, where we observe it arriving via polarized vesicular transport, indicating altered synapse organization. Indeed, cancer cells lacking EndoA3-mediated CIE or retromer form enlarged immune synapses that fail to sustain full T cell cytokine secretion, suggesting a compensatory attempt by T cells to overcome the defective synapse, while likely promoting more transient contacts that potentially favor serial killing. Together, these findings reveal that EndoA3-mediated CIE and retrograde transport act in concert in cancer cells to relocate immune synapse components via the Golgi, thereby fine-tuning the balance between cytotoxic T cell cytokine secretion and lytic activity. These insights contribute to a better understanding of the mechanisms governing immune synapse formation and organization, providing a necessary foundation for the long-term identification of new strategies to enhance T cell-mediated anti-tumor immunity.

Endophilin A3-mediated clathrin-independent endocytosis (EndoA3-mediated CIE) contributes to the internalization of immunoglobulin-like proteins, including key immune synapse components. Here, we identify ICAM1 as a novel EndoA3-dependent cargo, alongside ALCAM. We demonstrate that both proteins subsequently follow retromer-dependent retrograde transport to the trans -Golgi network (TGN) in cancer cells. From there, we propose that they undergo polarized redistribution to the plasma membrane, where they contribute to immune synapse formation between cancer cells and cytotoxic CD8 T cells. Disruption of EndoA3 or retromer components significantly affects the response of autologous cytotoxic CD8 T cells, as evidenced by reduced cytokine production and secretion, but increased lytic activity, while proliferation and later activation marker expression remain intact. This is accompanied by diminished ICAM1 density at the immune synapse, where we observe it arriving via polarized vesicular transport, indicating altered synapse organization. Indeed, cancer cells lacking EndoA3-mediated CIE or retromer form enlarged immune synapses that fail to sustain full T cell cytokine secretion, suggesting a compensatory attempt by T cells to overcome the defective synapse, while likely promoting more transient contacts that potentially favor serial killing. Together, these findings reveal that EndoA3-mediated CIE and retrograde transport act in concert in cancer cells to relocate immune synapse components via the Golgi, thereby fine-tuning the balance between cytotoxic T cell cytokine secretion and lytic activity. These insights contribute to a better understanding of the mechanisms governing immune synapse formation and organization, providing a necessary foundation for the long-term identification of new strategies to enhance T cell–mediated anti-tumor immunity.

To explore transcriptome differences between diploid and aneuploidy embryos, identify non-invasive screening targets for aneuploidy embryos, and establish a theoretical basis for a pathogenic model. RNA sequencing compared transcriptomes of diploid and aneuploid blastocysts, with GO and pathway analysis on differentially expressed genes. Fluorescent probes assessed clathrin-dependent and independent endocytosis in both cell types, while fluorescence quantitative PCR validated endocytosis abnormalities in early aneuploidy development. Additionally, free amino acid content was compared to show how aneuploidy genome imbalance affects endocytosis via changes in osmotic pressure. RNA sequencing revealed 9731 differentially expressed genes between normal diploids and aneuploidys, with 6134 up-regulated and 3597 down-regulated. KEGG analysis indicated these genes are mainly involved in endocytosis-related pathways. Six genes (PSD3, ARAP2, SMAP2, CBLC, AGAP1, SH3GLB1) showed significant differences (P < 0.05) in expression between diploid and aneuploidy groups. Molecular probe analysis and Fluorescence quantitative PCR resultsrevealed reduced clathrin-dependent endocytosis and increased clathrin-independent endocytosis in aneuploidy embryos compared to normal diploids(P < 0.05). Additionally, aneuploid embryos showed higher relative abundance of 14 free amino acids, particularly methionine. The study concludes that early transcriptome differences in aneuploid embryos are centered on endocytosis. Normal diploid embryos primarily use clathrin-dependent pathways, whereas aneuploid embryos favor clathrin-independent pathways. The endocytosis abnormalities in aneuploid cells are due to changes in intracellular osmotic pressure. This study provides a potential target for non-invasive detection of aneuploid embryos and lays a theoretical foundation for the establishment of a pathogenicity prediction model for aneuploid embryos.

Lipid nanoparticles (LNPs) play a critical role in the delivery of therapeutic messenger RNA (mRNA). Despite extensive efforts to optimize lipid formulations for in vivo delivery, efficacy of mRNA by LNPs remains suboptimal in many organs. Here, we demonstrate that LNP delivery efficacy is influenced by cellular metabolism, with the physiologic metabolome imposing constraints on mRNA expression from LNPs. Using an in vitro system, we found that simulated physiologic metabolic conditions led to the down-regulation of certain amino acid metabolic programs. Supplementation with an optimized formulation of methionine, arginine, and serine as an amino acid supplement (AAS) enhanced the uptake of LNPs and the expression of delivered mRNA cargo in epithelial cells in vitro. Coadministration of AAS with LNPs led to a 5- to 20-fold improvement in mRNA expression across various cell types and lipid formulations in vitro by promoting clathrin-independent carrier-mediated endocytosis. Delivery of mRNA by LNPs coadministered with AAS by multiple routes enhanced in vivo mRNA expression in preclinical models. Delivery of mRNA encoding growth hormone by LNPs with coadministration of AAS improved the liver growth hormone expression and the therapeutic outcomes in a model of inflammatory liver damage. Delivery of gene editing materials by LNP and AAS through an intratracheal route increased lung-targeted in vivo gene editing efficiency compared with LNP alone. The addition of an optimized AAS as a codelivered agent with LNPs may provide a simple strategy to broadly improve the efficacy of mRNA-based cell and gene therapies.

Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) effectively treat metastatic colorectal cancer (CRC); however, predicting response to these therapies remains challenging. Here, we aimed to identify key regulators of EGFR internalization as predictive biomarkers for anti-EGFR mAb therapy in CRC. CRC cell lines were treated with cetuximab and EGFR internalization was analyzed using siRNA knockdowns, inhibitors, and proteomic analyses. Key proteins mediating cetuximab-bound EGFR internalization were identified through immunoprecipitation and tandem mass spectrometry and validated using RT-PCR, co-immunoprecipitation, immunofluorescence, cell viability, and apoptosis assays. Immunohistochemistry was performed to correlate findings with clinical outcomes. Clathrin-dependent endocytosis mediated by Clathrin Heavy Chain was the primary pathway of cetuximab-bound EGFR internalization. Knockdown of clathrin-independent endocytosis genes or inhibition of macropinocytosis did not affect cetuximab-bound EGFR internalization. Ubiquitin Protein Ligase E3 Component N-Recognin 4 (UBR4) was identified as a critical mediator of EGFR degradation. UBR4 knockdown promoted EGFR recycling, enhanced cell proliferation, and reduced apoptosis in response to cetuximab. High UBR4 expression in CRC tissues correlated with better responses and longer progression-free survival in patients treated with anti-EGFR mAb therapy. UBR4 promotes clathrin-dependent EGFR degradation, enhancing anti-EGFR therapeutic efficacy, and may serve as a predictive biomarker in metastatic CRC.

Several trafficking pathways are operational at the plasma membrane, and both clathrin-dependent, and clathrin-independent endocytosis (CIE), can serve as virus entry portals. Our research has shown that the neurotropic flavivirus: Japanese encephalitis virus (JEV), infects neuronal cells via CIE. Here we have identified and characterized two essential host-factors for JEV trafficking in neuronal cells: Endophilin & Epidermal Growth Factor Receptor (EGFR). Through quantitative estimation of viral RNA copy number, we demonstrate that JEV entry in neuronal cells, was blocked by knock-down of Endophilin A isoforms, while activation of Endophilin-mediated endocytosis using a specific inhibitor of GSK-3β enhanced virus entry. Deletion mutants of Endophilin showed an essential role of SH3, BAR, H0 domains for virus entry. High resolution fluorescence imaging of virions showed overlap with Endophilin A2 puncta. Virus entry led to rearrangements of the actin cytoskeleton, and was highly sensitive to any pharmacological actin perturbation. Virus endocytosis activated EGFR, and the specific kinase inhibitors Erlotinib, and Gefitinib, reduced virus entry and replication in cultured cells and mouse primary cortical neurons. Silencing of EGFR, competitive inhibition with receptor ligand EGF, and EGFR specific antibodies significantly impaired JEV binding and entry, indicating the crucial role of its ligand binding domain for virus attachment/receptor interaction. EGFR colocalized with virions at early time-points of infection, and the ED3 domain of the JEV-envelope protein showed specific interaction with EGFR through Bio-layer interferometry (BLI). Our study provides evidence for JEV entry in neuronal cells through an endocytic pathway involving Endophilin and EGFR.

Spatiotemporal dynamics of AHA2 reveal that RALF1 induces its endocytosis and vacuolar degradation.

Endomembrane trafficking (ET) plays a crucial role in plant adaptation to environmental stresses, yet its involvement in endodermal root suberization remains poorly understood. Here, we show that disruption of clathrin-mediated endocytosis (CME) or canonical exocytosis led to an ectopic suberin deposition in the Arabidopsis root endodermis toward the root tip. Genetic disruption of endocytosis phenocopied the effects of the CME inhibitor ES9-17, while genetic disruption of clathrin-independent endocytosis led to reduced suberization, suggesting distinct, pathway-specific roles in regulating suberin deposition. Ectopic suberization upon CME inhibition required the CIFs-SGN3-SGN1-RBOHF/D signaling axis, independent of abscisic acid. Notably, CME disruption led to the accumulation of RBOHF in the plasma membrane, driving NADPH oxidase-dependent H2O2 accumulation inthe endodermis. Scavenging H2O2 or inhibiting NADPH oxidases abolished ET disruption-induced suberization, while exogenous H2O2 promoted it. Conversely, peroxidase activity inhibition reduced basal suberization but failed to suppress ET disruption-induced enhanced suberization, implicating reactive oxygen species (ROS) as a dominant driver. Our findings reveal a dual ET regulatory mechanism: exocytosis inhibition leads to suberization independently of known pathways, while CME impairment acts via RBOHF-mediated ROS to increase suberization on the endodermis. This study reveals that ET can control endodermal root suberization in Arabidopsis, linking membrane trafficking to apoplastic barrier formation through reactive oxygen species.

Glioblastoma is the most aggressive and lethal primary brain tumor in adults with the poorest prognosis, due to its high therapeutic resistance and rapid recurrence, which is closely associated with glioma stem cells (GSCs), which represent a critical therapeutic target in this refractory malignancy. As a classical calcium channel blocker (CCB), amlodipine exhibits exact anti-tumor effect independent of CCB activity. The present study further investigated its effects on GSCs and elucidated the relevant molecular mechanisms. Our results revealed that amlodipine exerted multifaceted inhibitory effects on GSCs, including reducing cell viability, self-renewal, invasiveness, and stemness, while enhancing apoptosis and suppressing intracranial tumor growth derived from GSCs. In contrast, other dihydropyridine CCBs and calcium chelators did not exhibit comparable anti-GSC effects at equivalent concentrations, suggesting that the anti-GSC activity of amlodipine is independent of calcium channel blockade. Mechanistically, amlodipine demonstrated high binding affinity to EGFR on the plasma membrane of GSCs, triggering its internalization via clathrin-independent lipid raft-mediated endocytosis. This process leaded to the lysosomal degradation of EGFR, resulting in the downregulation of EGFR protein levels and subsequent inhibition of downstream pro-survival signaling pathways. Taken together, our studies suggest that amlodipine suppresses GSCs-initiated tumor development via degrading EGFR and down-regulating its downstream pro-survival pathways, implying that amlodipine has novel potential as a therapeutic agent targeting GSCs in glioblastoma, deserving further investigations.

Endocytosis is a fundamental cellular process facilitated by diverse mechanisms. Remarkably, several distinct clathrin-independent endocytic processes have been identified and characterized following virus uptake into cells. For some, however, mechanistic execution and biological function remain largely unclear. This includes an endocytic process exploited by human papillomavirus type 16 (HPV16). Using HPV16, we examine how vesicles are formed by combining systematic cellular perturbations with electron and video microscopy. Cargo uptake occurs by uncoated, inward-budding pits. Mechanistically, vesicle scission is facilitated by actin polymerization controlled through the actin nucleation-promoting factor WASH. While WASH typically functions in conjunction with the retromer complex on endosomes during retrograde trafficking, endocytic vesicle formation is largely independent of retromer itself and the heterodimeric membrane-bending SNX-BAR retromer adaptor, thereby uncovering a role of WASH in endocytosis in addition to its canonical role in intracellular membrane trafficking.

Human noroviruses (HuNoVs), especially GII.4 strains, are the leading cause of acute viral gastroenteritis worldwide, yet no approved vaccines or antivirals exist. The pandemic GII.4 Sydney 2012 strain enters cells via membrane wounding and clathrin-independent carrier-mediated endocytosis, but it is unclear whether this entry mechanism is conserved across GII.4 variants. We compared early binding and entry of multiple GII.4 variants using wild-type and mutant GII.4 virus-like particles (VLPs) and modified human intestinal enteroid cultures. Only a subset of GII.4 variants, including GII.4 Sydney, form distinct, histo-blood group antigen (HBGA)-dependent capsid clusters on the cell surface. Clustering strains display significantly enhanced membrane wounding and endocytosis compared to nonclustering strains and outcompete nonclustering strains in replication assays exhibited by complete inhibition of GII.4 Sydney replication. Using mutant VLPs and an HBGA nonbinding mutant (R345A), we identified two residues, V333 and R339, in the VP1 protruding domain as critical mediators of clustering and entry. Mutations of these residues disrupt clustering and endocytosis without affecting HBGA binding, suggesting a role in postattachment processes. While clustering and endocytosis are contingent upon VLP binding to HBGAs, inhibitor studies show they are independent of host protein glycosylation and are driven by lipid raft remodeling regulated by cholesterol and ceramides. Quantitative analyses across multiple GII.4 variants reveal an apparent dichotomy between clustering and nonclustering phenotypes, with clustering variants exhibiting higher entry competence. This distinction offers insight into strain-specific cell entry mechanisms and may aid in identifying the elusive proteinaceous HuNoV cellular receptor(s) supporting targeted therapeutic development.

Breast cancer is the most common malignancy in women, with approximately 20-30% of all diagnosed cases characterized by HER2 overexpression. Several HER2-targeted cytotoxic conjugates have been developed, but their efficacy is limited. One of the main obstacles restraining the effectiveness of HER2-specific cytotoxic conjugates is their low internalization, as HER2 is immobile mainly on the cell surface. Therefore, there is a need to develop novel HER2-selective cytotoxic conjugates that will overcome HER2 immovability and, by this, ensure efficient drug delivery into HER2-overexpressing cancer cells. Here, we present a novel system for generating high affinity, self-assembling, inherently fluorescent, and multivalent HER2 ligands. The developed HER2-specific ligands largely overcome the innate stability of HER2 in the plasma membrane by triggering clathrin-independent aggregation-dependent endocytosis of the receptor. To exploit the pro-endocytic potential of developed proteins, we constructed the tetravalent fluorescent cytotoxic conjugate TetraFHER2-vcMMAE and demonstrated its high potency and selectivity against HER2+ breast cancer cells.

Gene therapy is a promising clinical approach for treating or preventing genetic diseases by directly targeting disease-causing mutations. Despite the potential for gene therapy in addressing a broad range of genetic diseases, the development of these techniques remains in its early stages. A key challenge in the field is the development of approaches that efficiently deliver modified genetic material to intended biological targets, but minimize degradation and off-target effects. Biomedical polymeric nanoparticles (PNPs) can enhance gene therapy delivery by encapsulating, protecting, and releasing therapeutic compounds within target cells. However, their clinical translation is hindered by poor efficacy and storage instability. To address these challenges, we formulated Envoyer nanoparticles, a novel natural polymer-based delivery system. Here, we evaluate the stability and transfection efficiency of Envoyer nanoparticles in multiple human cell lines. In HEK293T cells, Envoyer nanoparticles (50–70 nm) encapsulating green fluorescent protein (GFP) plasmid DNA (pDNA) achieved a transfection efficiency of >80%, outperforming lipofectamine controls (∼60%). In PANC1 pancreatic cancer cells, known for being difficult to transfect, Envoyer nanoparticles also demonstrated superior efficacy compared to lipofectamine controls. Notably, commonly used commercially available nanoparticles failed to produce GFP expression under similar conditions. Preliminary mechanistic studies suggest that Envoyer nanoparticle internalization occurs via clathrin-independent endocytosis. Furthermore, we show that Envoyer nanoparticles maintain stability and transfection efficiency after storage for 2 months at 4 °C and −80 °C. Collectively, these findings highlight the potential of Envoyer nanoparticles as a stable and efficient gene delivery platform for future clinical applications in gene therapy.

Small extracellular vesicles (sEVs) play crucial roles in intercellular communication. However, the internalization of individual sEVs by recipient cells has not been directly observed. Here, we examined these mechanisms using state-of-the-art imaging techniques. Single-molecule imaging shows that tumor-derived sEVs can be classified into several subtypes. Simultaneous single-sEV particle tracking and observation of super-resolution movies of membrane invaginations in living cells reveal that all sEV subtypes are internalized via clathrin-independent endocytosis mediated by galectin-3 and lysosome-associated membrane protein-2C, while some subtypes that recruited raft markers are internalized through caveolae. Integrin β1 and talin-1 accumulate in recipient cell plasma membranes beneath all sEV subtypes. Paracrine, but not autocrine, sEV binding triggers Ca2+ mobilization induced by the activation of Src family kinases and phospholipase Cγ. Subsequent Ca2+-induced activation of calcineurin–dynamin promotes sEV internalization, leading to the recycling pathway. Thus, we clarified the detailed mechanisms of sEV internalization driven by paracrine adhesion signaling.

Continuous interaction between chimeric antigen receptor (CAR) T cell (CART) and tumors often result in CART dysfunction and tumor escape. We observed that tumors can take up CAR molecules, leaving CARTs without surface-expressed CARs and thus unable to kill tumors after prolonged exposure. Overexpression of Rab5 resulted in augmented clathrin-independent endocytosis, preventing loss of surface-expressed CARs, and enhanced CART activity. Interestingly, we observed membrane protrusions on the CART cell surface which disappeared after multiple tumor challenges. Rab5 maintained these protrusions after repeated tumor engagements and their presence correlated with effective tumor clearance, suggesting a link between endocytosis, membrane protrusions, and cytolytic activity. In vivo , Rab5-expressing CARTs demonstrated improved activity and were able to clear an otherwise refractory mesothelin-expressing solid cancer in humanized mice by maintaining CAR surface expression within the tumor. Thus, pairing Rab5 with CAR expression could improve the clinical efficacy of CART therapy. Highlights "CAR-jacking" occurs when surface CAR is internalized by target tumor cells.Rab5 overexpression prevents "CAR-jacking" and enhances CART function.Rab5 promotes CAR endocytic recycling and maintains membrane protrusions.Rab5-expressing CARTs exhibit enhanced therapeutic efficacy against solid tumors.

In this study, we used cryoelectron microscopy to determine the structures of the Flotillin protein complex, part of the Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) superfamily, from cell-derived vesicles without detergents. It forms a right-handed helical barrel consisting of 22 pairs of Flotillin1 and Flotillin2 subunits, with a diameter of 32 nm at its wider end and 19 nm at its narrower end. Oligomerization is stabilized by the C terminus, which forms two helical layers linked by a β-strand, and coiled-coil domains that enable strong charge-charge intersubunit interactions. Flotillin interacts with membranes at both ends; through its SPFH1 domains at the wide end and the C terminus at the narrow end, facilitated by hydrophobic interactions and lipidation. The inward tilting of the SPFH domain, likely triggered by phosphorylation, suggests its role in membrane curvature induction, which could be connected to its proposed role in clathrin-independent endocytosis. The structure suggests a shared architecture across the family of SPFH proteins and will promote further research into Flotillin's roles in cell biology.

Fibroblast growth factor receptor 1 (FGFR1) is a N-glycosylated cell surface receptor tyrosine kinase, which upon recognition of specific extracellular ligands, fibroblast growth factors (FGFs), initiates an intracellular signaling. FGFR1 signaling ensures homeostasis of cells by fine-tuning essential cellular processes, like differentiation, division, motility and death. FGFR1 activity is coordinated at multiple steps and unbalanced FGFR1 signaling contributes to developmental diseases and cancers. One of the crucial control mechanisms over FGFR1 signaling is receptor endocytosis, which allows for rapid targeting of FGF-activated FGFR1 to lysosomes for degradation and the signal termination. We have recently demonstrated that N-glycans of FGFR1 are recognized by a precise set of extracellular galectins, secreted and intracellular multivalent lectins implicated in a plethora of cellular processes and altered in immune responses and cancers. Specific galectins trigger FGFR1 clustering, resulting in activation of the receptor and in initiation of intracellular signaling cascades that shape the cell physiology. Although some of galectin family members emerged recently as key players in the clathrin-independent endocytosis of specific cargoes, their impact on endocytosis of FGFR1 was largely unknown.Here we assessed the contribution of extracellular galectins to the cellular uptake of FGFR1. We demonstrate that only galectin-1 induces internalization of FGFR1, whereas the majority of galectins predominantly inhibit endocytosis of the receptor. We focused on three representative galectins: galectin-1, -7 and -8 and we demonstrate that although all these galectins directly activate FGFR1 by the receptor crosslinking mechanism, they exert different effects on FGFR1 endocytosis. Galectin-1-mediated internalization of FGFR1 doesn’t require galectin-1 multivalency and occurs via clathrin-mediated endocytosis, resembling in this way the uptake of FGF/FGFR1 complex. In contrast galectin-7 and -8 impede FGFR1 endocytosis, causing stabilization of the receptor on the cell surface and prolonged propagation of the signals. Furthermore, using protein engineering approaches we demonstrate that it is possible to modulate or even fully reverse the endocytic potential of galectins.

Several bacterial toxins and viruses can deform membranes through multivalent binding to lipids for clathrin-independent endocytosis. However, it remains unclear, how membrane deformation and endocytic internalization are mechanistically linked. Here we show that many lipid-binding virions induce membrane deformation and clathrin-independent endocytosis, suggesting a common mechanism based on multivalent lipid binding by globular particles. We create a synthetic cellular system consisting of a lipid-anchored receptor in the form of GPI-anchored anti-GFP nanobodies and a multivalent globular binder exposing 180 regularly-spaced GFP molecules on its surface. We show that these globular, 40 nm diameter, particles bind to cells expressing the receptor, deform the plasma membrane upon adhesion and become endocytosed in a clathrin-independent manner. We explore the role of the membrane adhesion energy in endocytosis by using receptors with affinities varying over 7 orders of magnitude. Using this system, we find that once a threshold in adhesion energy is overcome to allow for membrane deformation, endocytosis occurs reliably. Multivalent, binding-induced membrane deformation by globular binders is thus sufficient for internalization to occur and we suggest it is the common, purely biophysical mechanism for lipid-binding mediated endocytosis of toxins and pathogens.

Multiple endocytic processes operate in cells in tandem for the uptake of multiple cargoes, metabolites, and signaling molecules that are involved in diverse cellular functions including cell adhesion and migration. The best studied endocytic process involves the formation of a well-defined cytoplasmic coat at sites of uptake made of clathrin and its interacting partners. Galectin-3 (Gal3), an endogenous lectin, binds to glycosylated membrane receptors and glycosphingolipids (GSLs) to drive membrane bending, leading to the formation of tubular membrane invaginations which undergo scission to form a morphologically distinct class of uptake structures, termed clathrin-independent carriers (CLICs). This mechanism has been termed the GlycoLipid-Lectin (GL-Lect) hypothesis. Which components from cytoskeletal machinery are involved in the scission of CLICs remains yet to be explored. In this study, we propose that dynein, a retrograde motor protein, is recruited onto Gal3-induced tubular endocytic pits and provides the pulling force to for friction driven scission. Uptake of Gal3 and its cargoes (CD98/CD147) is significantly dependent on dynein activity, whereas the uptake of transferrin (a marker for clathrin-mediated endocytosis) is only slightly affected upon dynein inhibition. Dynein inhibition also affects cellular organelle distribution, 3D cell invasion and wound healing. Our study thereby reveals functions of dynein in individual and collective cell migration in 2D and 3D that are tightly coupled to endocytic processes in cells.

Altered platelet-megakaryocyte endocytosis and trafficking of albumin and fibrinogen in RUNX1 haplodeficiency