Endosomes and vesicles

Not one body but a route. The sorting station changes its marker protein rather than handing cargo to a different organelle, and the coat at the start of the route is not always a round cage.

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Where endocytosed material arrives

internalised receptor-ligand complexes and other endocytosed proteins arrive at the Rab5-positive early endosome, where they are sorted

general · review · Solinger JA and colleagues 2025, Biochem Soc Trans · source

What decides the fate of a cargo

a ubiquitin mark: marked cargo is bound by ESCRT-0 and ESCRT-I to begin degradation, and the rest is recycled back to the plasma membrane or to the trans-Golgi network

general · review · Solinger JA and colleagues 2025, Biochem Soc Trans · source

Maturation is a swap, not a handover

to degrade its cargo the early endosome matures into the multivesicular body, which requires the Rab5-to-Rab7 conversion mediated by the RABEX5-MON1/CCZ1 RabGEF cascade; cargo is packaged into intraluminal vesicles by ESCRT-III and Vps4, and the matured body fuses with a lysosome

general · review · Solinger JA and colleagues 2025, Biochem Soc Trans · source

The two halves are coordinated

loss of early ESCRTs gave enlarged Rab5-positive endosomes and blocked the Rab conversion, and reducing ubiquitinated cargo relieved it, so cargo corralling by the ESCRTs is upstream of the conversion and ESCRT-0 with ubiquitinated cargo may act as a timer for when it begins

not stated in the abstract; the gene names given, RABX-5 and SAND-1/CCZ-1, are the Caenorhabditis elegans ones · genetic loss of function with endosome imaging · Ott DP and colleagues 2025, EMBO J · source

The coat is conserved

clathrin coat proteins and their honeycomb lattice structures are highly conserved across mammals, yeasts and plants, and endocytic initiation requires similar protein domains in all three

mammals, yeasts, plants · review · Johnson A and colleagues 2024, J Cell Sci · source

The coat is not always a round cage

clathrin assembles into a range of membrane-associated architectures whose geometry, dynamics and function differ by compartment: curved coated pits at the plasma membrane and trans-Golgi network, extended flat lattices and plaques at the cell surface, coats on endosomal sorting domains, and tubular assemblies associated with three-dimensional migration

general · review of electron microscopy and ultrastructural work · Benoist M and colleagues 2026, Traffic · source

Not universal: membrane bending

the mechanisms that drive coated vesicle formation diverge between systems, and plant endocytosis occurs independently of actin, so assumptions about the mechanism carried from one organism to another should be made with caution

mammals, yeasts, plants · review · Johnson A and colleagues 2024, J Cell Sci · source

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Sizes and counts

no abstract read for this page gives an endosome diameter, a vesicle diameter, an intraluminal vesicle count or a number of clathrin triskelia with a method. Everything in the copy is proportioned for legibility, not measured.

How many polygons in the cage

the copy builds the coat by spreading points over a sphere and joining each to its nearest neighbours, which reads as a lattice. The pentagon and hexagon counts of a real clathrin cage are not taken from any source read here and are not claimed.

COPI and COPII

the other two coat systems of the cell are not shown and not described. No source was read for them for this page, so they are absent rather than guessed at.

Behind the copy

The endosomal system is a route rather than a single body. Material taken in at the plasma membrane arrives at the Rab5-positive early endosome and is sorted there: cargo carrying a ubiquitin mark is bound by ESCRT-0 and ESCRT-I and set aside for degradation, and the rest is recycled back to the plasma membrane or to the trans-Golgi network. To degrade its cargo the early endosome has to mature into a late endosomal structure, the multivesicular body, and that maturation is a swap of marker protein on the same body: Rab5 is replaced by Rab7 through the RABEX5-MON1/CCZ1 guanine nucleotide exchange factor cascade. The cargo destined for degradation is packaged into intraluminal vesicles by ESCRT-III and Vps4, and the matured body finally fuses with a lysosome. The two halves of that process are not independent: cargo corralling by the ESCRTs sits upstream of the Rab conversion, so ESCRT-0 and ubiquitinated cargo may act as a timer for when the conversion begins. The coat at the start of the route is also less uniform than the picture of a round cage suggests. Clathrin coat proteins and their honeycomb lattice structures are highly conserved, but clathrin assembles into a range of membrane-associated architectures whose geometry and function differ by compartment: curved coated pits at the plasma membrane and trans-Golgi network, extended flat lattices and plaques at the cell surface, coats on endosomal sorting domains, and tubular assemblies associated with three-dimensional migration.

source 1, source 2, source 3, source 4

Real pictures

Gallery and papers in the library

Panel D (EEA1): early endosome marker as magenta puncta, inset with arrowheads. composite of 14 immunofluorescence panels, mouse choroid plexus epithelial cells; magenta channel is the named organelle marker Ono, Shishido, Yamagishi et al 2026, The FEBS Journal, CC BY 4.0 · source · immunofluorescence, composite figure

Enlargement and altered distribution of early endosomes in SORL1 p.Y1816C and KO neurons and organoids. (A) Representative immunofluorescence images showing EEA1-positive early endosomes in WT, SORLA KO, and KI 2D neurons at day 20 and 3D cerebral organoids at day 60; (B) Size distribution of EEA1+ puncta in 2D neurons, showing the proportion of standard-sized (<=0.5 um2) and enlarged (>0.5 um2) EEA1-positive endosomes across genotypes. Lep, Plesingrova, Sedmik et al 2026, Alzheimer's and Dementia, CC BY 4.0 · source · figure from an open-access paper

STX12 depletion disrupts early endocytic trafficking in GSCs. Confocal immunofluorescence showing colocalization of STX12 (green) with the early endosome marker EEA1 (red) in GSCs. Nuclear staining with DAPI is shown in blue. Corresponding higher-magnification insets are shown below. Scale bars: 10 um. Maghe, Barbach, Andre-Gregoire et al 2026, Traffic (Copenhagen, Denmark), CC BY 4.0 · source · figure from an open-access paper

Localization of cell-cell junction components during de novo epithelial polarization and generation of Rab11a-KO MDCK cell lines. (A, B) Single MDCK cells after 12 hr of culture in Matrigel. Immunostaining signals of the indicated markers are shown: centrosome marker gamma-tubulin, polarity protein Par3, acetyl-tubulin, actin, E-cadherin (E-cad), ZO-1, and DAPI. Single confocal sections through the middle of cysts are displayed. Wang, Lin, Tang et al 2026, eLife, CC BY 4.0 · source · figure from an open-access paper

NoxO1 and Erbin cooperatively regulate endosomal pathways in Hek293 cells. Analyses of endosomal markers in resting cells with or without Erbin knock out (Erbin KO) overexpressing an empty vector or NoxO1 (OE): Early endosome antigen 1 (EEA1) for early endosomes, n = 6; Ras-related protein 11 (Rab11) for recycling endosomes, n = 6; Ras-related protein 7 (Rab7) for late endosomes, n = 3; Lysosome a Hebchen, Herwig, Schader et al 2026, Redox Biology, CC BY 4.0 · source · figure from an open-access paper

Co-localization dynamics of EGF-QDs with specific endocytic markers in cancer cell lines in control conditions and after BafA1 pretreatment. (A) Confocal images of HeLa cells that were incubated with EGF-QDs (red). The cells were then fixed and immunostained with an anti-EEA1, anti-Rab7, anti-CD63, and anti-Lamp1 antibodies (green). Each image is a maximum intensity projection of a Z-stack onto a single image, representative of the corresponding time point in at least three independent experiments. The white lines in the images delineate the boundaries of the cells and nuclei according to differential interference contrast. Scale bars: 10 μm. (B, C) Manders' coefficients (M1) of co-localization between EGF-QDs and specific endocytic markers in HeLa cells (B) and A549 cells (C). Salova, Belyaeva, Litvinov et al 2025, International Journal of Molecular Sciences, CC BY 4.0 · source · figure from an open-access paper

Rabex5 recruitment to endosomes depends on ubiquitin binding in mammalian cells. (A) Enlarged Rab5 (magenta) early endosomes become smaller when Rabex5 carries mutations in its ubiquitin binding site. Mutated Rabex5 (green) is predominantly cytoplasmic. Similar effects can be seen in a CCZ1 KO background where Rab conversion is blocked. Ott, Desai, Solinger et al 2025, The EMBO Journal, CC BY 4.0 · source · figure from an open-access paper

STX12 depletion disrupts early endocytic trafficking in GSCs. (C) Confocal imaging of EEA1 (red), RAB5 (green), and GM130 (green) in control and STX12-depleted cells, in sic or siSTX12-transfected cells. Nuclear staining with DAPI is shown in blue. Corresponding higher-magnification insets with inverted grayscale are shown on the right. Scale bars: 10 um. Maghe, Barbach, Andre-Gregoire et al 2026, Traffic, CC BY 4.0 · source · figure from an open-access paper

SNX6-SNX2 are distributed with DIO3 during endocytosis. Confocal immunofluorescence microscopy of ES-2 cells under 100 µM MDC for 3 h, in DMSO and MDC conditions: DIO3 (red) with (D) EEA1 (far red, shown in cyan) and (E) RAB7 (green). Scale bars: 20 μm. Maman-Shinar, Vanmak, Bern et al 2026, Cellular Oncology, CC BY 4.0 · source · figure from an open-access paper

Enlargement and altered distribution of early endosomes in SORL1 p.Y1816C and KO neurons and organoids. (D) Representative TEMs of EL and ED endosomes in WT, KI, and KO neurons; Lep, Plesingrova, Sedmik et al 2026, Alzheimer's & Dementia, CC BY 4.0 · source · figure from an open-access paper

Dynamics of recycling endosomes (REs) in GBF1 M832L cells. a , b Localization of REs in wild-type ( a ) and GBF1 M832L cells ( b ) before (left) and 30 min after BFA administration (right). Magnified black-and-white single-channel images of the insets are shown in the right panels. The images show Ruby::GM130 in red, GalT::iRFP713 in blue, and NeonGreen::Rab11a in green. Takiguchi, Shek, Sasaki et al 2026, Nature Communications, CC BY 4.0 · source · figure from an open-access paper

Cryo-electron tomography observation of hemifused vesicles at the leading edge of cultured cells. b Representative cryo-electron tomogram slice of the border of a COS-7 cell highlighting cytoskeletal components, endosome-like vesicles (En), a clathrin-coated vesicle (CV), and a hemifusome (HF). A single bilayer or hemifusion diaphragm separates the hemifused vesicles. The larger vesicle has a fine granular content, and the smaller hemifused vesicle has a smooth translucent lumen (*). The arrowhead points to the proteolipid particle and arrow points to the nanodroplet at the rim of the hemifusion diaphragm (representative from at least 10 tomograms). Scale bar: 100 nm. Tavakoli, Hu, Ebrahim et al 2025, Nature Communications, CC BY 4.0 · source · figure from an open-access paper

Ultrastructural evidence of exosome release from myoblast cells following shockwave treatment. Representative EM micrographs illustrating the progression of exosome secretion from a C2C12 cell following SW treatment. A multivesicular body (MVB) is observed as a membranous structure in close proximity to the plasma membrane (PM), characterized by a single limiting membrane enclosing exosomes that appear as intraluminal vesicles (ILVs, arrows) (A). MVB migrates and fuses with the plasma membrane (B), leading to the exocytic release of exosomes into the extracellular space (C). The fusion profile between the MVB and the plasma membrane can be observed in proximity to the released exosomes (D). M: mitochondrion. Scale bar: A--D = 175 nm; B--C = 350 nm. (mouse (C2C12 myoblast, shockwave-treated); FIGURE 2, full figure (panels A-D; MVB exocytosis sequence).) Ryskalin, Fulceri, Germelli et al 2026, The FASEB Journal, CC BY 4.0 · source · figure from an open-access paper, transmission electron microscopy (TEM)

HK2 cells were transiently transfected with plasmids carrying the indicated EGFP-WIPI2 variants with mCherry-RAB5 or RFP-RAB4. (human (HK2 kidney); Figure 4 -- figure supplement 2, panels A, B (confocal fluorescence; micrograph section rows 30-943 of figure).) De Leo, Mayer, Bottanelli et al 2026, eLife, CC BY 4.0 · source · figure from an open-access paper, confocal fluorescence (EGFP-WIPI2, mCherry-RAB5, RFP-RAB4)

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