Endosome
Endosomes are a collection of intracellular sorting
Endosomes can be classified as early, sorting, or late depending on their stage post internalization.[1] Endosomes represent a major sorting compartment of the endomembrane system in cells.[2]
Function
Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome.[2] For example, low-density lipoprotein (LDL) is taken into the cell by binding to the LDL receptor at the cell surface. Upon reaching early endosomes, the LDL dissociates from the receptor, and the receptor can be recycled to the cell surface. The LDL remains in the endosome and is delivered to lysosomes for processing. LDL dissociates because of the slightly acidified environment of the early endosome, generated by a vacuolar membrane proton pump V-ATPase. On the other hand, epidermal growth factor (EGF) and the EGF receptor have a pH-resistant bond that persists until it is delivered to lysosomes for their degradation. The mannose 6-phosphate receptor carries ligands from the Golgi destined for the lysosome by a similar mechanism.
Types
There are three different types of endosomes: early endosomes, late endosomes, and recycling endosomes.[2] They are distinguished by the time it takes for endocytosed material to reach them, and by markers such as Rabs.[3] They also have different morphology. Once endocytic vesicles have uncoated, they fuse with early endosomes. Early endosomes then mature into late endosomes before fusing with lysosomes.[4][5]
Early endosomes mature in several ways to form late endosomes. They become increasingly acidic mainly through the activity of the V-ATPase.[6] Many molecules that are recycled are removed by concentration in the tubular regions of early endosomes. Loss of these tubules to recycling pathways means that late endosomes mostly lack tubules. They also increase in size due to the homotypic fusion of early endosomes into larger vesicles.[7] Molecules are also sorted into smaller vesicles that bud from the perimeter membrane into the endosome lumen, forming intraluminal vesicles (ILVs); this leads to the multivesicular appearance of late endosomes and so they are also known as multivesicular endosomes or multivesicular bodies (MVBs). Removal of recycling molecules such as transferrin receptors and mannose 6-phosphate receptors continues during this period, probably via budding of vesicles out of endosomes.[4] Finally, the endosomes lose RAB5A and acquire RAB7A, making them competent for fusion with lysosomes.[7]
Fusion of late endosomes with lysosomes has been shown to result in the formation of a 'hybrid' compartment, with characteristics intermediate of the two source compartments.[8] For example, lysosomes are more dense than late endosomes, and the hybrids have an intermediate density. Lysosomes reform by recondensation to their normal, higher density. However, before this happens, more late endosomes may fuse with the hybrid.
Some material recycles to the plasma membrane directly from early endosomes,[9] but most traffics via recycling endosomes.
- Early endosomes consist of a dynamic tubular-vesicular network (vesicles up to 1 µm in diameter with connected tubules of approx. 50 nm diameter). Markers include RAB5A and RAB4, Transferrin and its receptor and EEA1.
- Late endosomes, also known as MVBs, are mainly spherical, lack tubules, and contain many close-packed intraluminal vesicles. Markers include RAB7, RAB9, and mannose 6-phosphate receptors.[10] In addition to this, the late endosomal membrane (and consequently the lysosome) contains a peculiar and unique lipid named BMP or LBPA, which is not found in any other organelle membrane.[11][12]
- Recycling endosomes are concentrated at the microtubule organizing center and consist of a mainly tubular network. Marker; RAB11.[13]
More subtypes exist in specialized cells such as polarized cells and macrophages.
Late endosomes/MVBs are sometimes called endocytic carrier vesicles, but this term was used to describe vesicles that bud from early endosomes and fuse with late endosomes. However, several observations (described above) have now demonstrated that it is more likely that transport between these two compartments occurs by a maturation process, rather than vesicle transport.
Another unique identifying feature that differs between the various classes of endosomes is the lipid composition in their membranes. Phosphatidyl inositol phosphates (PIPs), one of the most important
Pathways
There are three main compartments that have pathways that connect with endosomes. More pathways exist in specialized cells, such as
There is no consensus as to the exact nature of these pathways, and the sequential route taken by any given cargo in any given situation will tend to be a matter of debate.
Golgi to/from endosomes
Vesicles pass between the Golgi and endosomes in both directions. The
Plasma membrane to/from early endosomes (via recycling endosomes)
Molecules are delivered from the plasma membrane to early endosomes in
Late endosomes to lysosomes
Transport from late endosomes to lysosomes is, in essence, unidirectional, since a late endosome is "consumed" in the process of fusing with a lysosome (sometimes called endolysosome
See also
References
- S2CID 31539542.
- ^ PMID 8970738.
- S2CID 33236823.
- ^ PMID 8601581.
- PMID 10751143.
- PMID 18648502.
- ^ PMID 16143105.
- PMID 9456319.
- PMID 6309862.
- PMID 16781134.
- PMID 12065580.
- ^ PMID 19857945.
- PMID 8922376.
- PMID 19008921.
- PMID 16428780.
- PMID 18216768.
- S2CID 4421550.
- PMID 15511083.
- PMID 19696797.
- PMID 11756475.
- S2CID 22770514.
- PMID 2874839.
- PMID 34611326.
- PMID 33324224.
- PMID 14570567.
- PMID 18222686.
- Alberts, Bruce; et al. (2004). Essential Cell Biology (2nd ed.). New York, NY: Garland Science. ISBN 978-0-8153-3480-4.