Endosome
Encyclopedia
In biology
, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic
membrane transport pathway from the plasma membrane to the lysosome
. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane. Molecules are also transported to endosomes from the Golgi
and either continue to lysosomes or recycle back to the Golgi. Furthermore, molecules can be directed into vesicles that bud from the perimeter membrane into the endosome lumen. Therefore, endosomes represent a major sorting compartment of the endomembrane system
in cells. Endosomes are approximately 500 nm
in diameter when fully mature.
at the cell surface. On 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 membrane proton pump V-ATPase
. On the other hand, 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.
. 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.
Early endosomes mature in several ways to form late endosomes. They become increasingly acidic mainly through the activity of the V-ATPase. 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. Molecules are also sorted into smaller vesicles that bud from the perimeter membrane into the endosome lumen, forming lumenal vesicles; this leads to the multivesicular appearance of late endosomes and so they are also known as 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. Finally, the endosomes lose RAB5 and acquire RAB7, making them competent for fusion with lysosomes.
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. 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, but most traffics via recycling endosomes.
More subtypes exist in specialized cells such as polarized cells and macrophage
s.
Phagosomes, macropinosomes and autophagosomes mature in a manner similar to endosomes, and may require fusion with normal endosomes for their maturation. Some intracellular pathogens subvert this process, for example, by preventing RAB7 acquisition.
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.
cells, a special process called transcytosis allows some materials to enter one side of a cell and exit from the opposite side. Also, in some circumstances, late endosomes/MVBs fuse with the plasma membrane instead of with lysosomes, releasing the lumenal vesicles, now called exosomes
, into the extracellular medium.
It should be noted that 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.
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
membrane transport pathway from the plasma membrane to the lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane. Molecules are also transported to endosomes from the Golgi
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
and either continue to lysosomes or recycle back to the Golgi. Furthermore, molecules can be directed into vesicles that bud from the perimeter membrane into the endosome lumen. Therefore, endosomes represent a major sorting compartment of the endomembrane system
Endomembrane system
The endomembrane system is composed of the different membranes that are suspended in the cytoplasm within a eukaryotic cell. These membranes divide the cell into functional and structural compartments, or organelles...
in cells. Endosomes are approximately 500 nm
Nanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...
in diameter when fully mature.
Function
Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, LDL is taken into the cell by binding the LDL receptorLDL receptor
The Low-Density Lipoprotein Receptor is a mosaic protein of ~840 amino acids that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles...
at the cell surface. On 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 membrane proton pump V-ATPase
V-ATPase
Vacuolar-type H+-ATPase is a highly conserved evolutionarily ancient enzyme with remarkably diverse functions in eukaryotic organisms. V-ATPases acidify a wide array of intracellular organelles and pump protons across the plasma membranes of numerous cell types...
. On the other hand, 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
Mannose 6-phosphate receptor
In the fields of biochemistry and cell biology, mannose 6-phosphate receptors are proteins that bind newly synthesized lysosomal hydrolases in the trans-Golgi network and deliver them to pre-lysosomal compartments. There are two different MPRs, one of ~300kDa and a smaller, dimeric receptor of...
carries ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
from the Golgi destined for the lysosome by a similar mechanism.
Types
Endosomes comprise three different compartments: early endosomes, late endosomes, and recycling endosomes. They are distinguished by the time it takes for endocytosed material to reach them, and by markers such as rabsRab (G-protein)
The Rab family of proteins is a member of the Ras superfamily of monomeric G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab GTPases regulate many steps of membrane traffic, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane...
. They also have different morphology. Once endocytic
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
vesicles have uncoated, they fuse with early endosomes. Early endosomes then mature into late endosomes before fusing with lysosomes.
Early endosomes mature in several ways to form late endosomes. They become increasingly acidic mainly through the activity of the V-ATPase. 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. Molecules are also sorted into smaller vesicles that bud from the perimeter membrane into the endosome lumen, forming lumenal vesicles; this leads to the multivesicular appearance of late endosomes and so they are also known as 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. Finally, the endosomes lose RAB5 and acquire RAB7, making them competent for fusion with lysosomes.
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. 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, 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 RAB5 and RAB4, TransferrinTransferrinTransferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
and its receptorTransferrin receptorTransferrin receptor is a carrier protein for transferrin. It is needed for the import of iron into the cell and is regulated in response to intracellular iron concentration...
and EEA1.
- Late Endosomes, also known as MVBs, are mainly spherical, lack tubules, and contain many close-packed lumenal vesicles. Markers include RAB7, RAB9, and mannose 6-phosphate receptors.
- Recycling Endosomes are concentrated at the microtubule organizing center and consist of a mainly tubular network. Marker; RAB11.
More subtypes exist in specialized cells such as polarized cells and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s.
Phagosomes, macropinosomes and autophagosomes mature in a manner similar to endosomes, and may require fusion with normal endosomes for their maturation. Some intracellular pathogens subvert this process, for example, by preventing RAB7 acquisition.
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.
Pathways
There are three main compartments that have pathways that connect with endosomes. More pathways exist in specialized cells, such as melanocytes and polarized cells. For example, in epithelialEpithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
cells, a special process called transcytosis allows some materials to enter one side of a cell and exit from the opposite side. Also, in some circumstances, late endosomes/MVBs fuse with the plasma membrane instead of with lysosomes, releasing the lumenal vesicles, now called exosomes
Exosome (vesicle)
Exosomes are 30-90 nm vesicles secreted by a wide range of mammalian cell types. First discovered in maturing mammalian reticulocytes, they were shown to be a mechanism for selective removal of many plasma membrane proteins. These proteins are lost or reduced in amount, without concomitant...
, into the extracellular medium.
It should be noted that 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 GGAGGAGGA or Gga may refer to:*Gereja Generasi Apostolik, Apostolic Generation Church in English*Girl Guides Australia*Good girl art*Goemon's Great Adventure, a 1998 Nintendo 64 video game...
s and AP-1AP1G1AP-1 complex subunit gamma-1 is a protein that in humans is encoded by the AP1G1 gene.-Interactions:AP1G1 has been shown to interact with RABEP1, AP1B1, Synaptophysin, AP1M1, NECAP2, AP1S1 and AP1GBP1.-Further reading:...
clathrin-coated vesicle adaptors make vesicles at the Golgi that carry molecules to endosomes. In the opposite direction, retromerRetromerThe retromer is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to the trans-Golgi network .-Discovery:...
generates vesicles at early endosomes that carry molecules back to the Golgi. Some studies describe a retrograde traffic pathway from late endosomes to the Golgi that is mediated by Rab9 and TIP47, but other studies dispute these findings. Molecules that follow these pathways include the Mannose-6-phosphate receptors that carry lysosomal hydrolases to the endocytic pathway. The hydrolases are released in the acidic environment of endosomes, and the receptor is retrieved to the Golgi by retromer and Rab9.
- Plasma membrane to/from early endosomes (via recycling endosomes). Molecules are delivered from the plasma membrane to early endosomes in endocyticEndocytosisEndocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
vesicles. Molecules can be internalized via receptor-mediated endocytosisReceptor-mediated endocytosisReceptor-mediated endocytosis , also called clathrin-dependent endocytosis, is a process by which cells internalize molecules by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized.-Process:After the binding of a...
in clathrin-coated vesicles. Other types of vesicles also form at the plasma membrane for this pathway, including ones utilising caveolinCaveolaeIn biology, caveolae , which are a special type of lipid raft, are small invaginations of the plasma membrane in many vertebrate cell types, especially in endothelial cells and adipocytes....
. Vesicles also transport molecules directly back to the plasma membrane, but many molecules are transported in vesicles that first fuse with recycling endosomes. Molecules following this recycling pathway are concentrated in the tubules of early endosomes. Molecules that follow these pathways include the receptorsReceptor (biochemistry)In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
for LDL, the growth hormone EGFEGFEGF can refer to several things:*Epidermal growth factor, a growth factor in biology*Exponential generating function, a function in mathematics*European Gendarmerie Force, a European intervention force...
, and the iron transport protein transferrin. Internalization of these receptors from the plasma membrane occurs by receptor-mediated endocytosis. LDL is released in endosomes because of the lower pH, and the receptor is recycled to the cell surface. CholesterolCholesterolCholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
is carried in the blood primarily by (LDL), and transport by the LDL receptor is the main mechanism by which cholesterol is taken up by cells. EGFRs are activated when EGF binds. The activated receptors stimulate their own internalization and degradation in lysosomes. EGF remains bound to the EGFR once it is endocytosed to endosomes. The activated EGFRs stimulate their own ubiquitination, and this directs them to lumenal vesicles (see below) and so they are not recycled to the plasma membrane. This removes the signaling portion of the protein from the cytosol and thus prevents continued stimulation of growth - in cells not stimulated with EGF, EGFRs have no EGF bound to them and therefore recycle if they reach endosomes. Transferrin also remains associated with its receptor, but, in the acidic endosome, iron is released from the transferrin, and then the iron-free transferrin (still bound to the transferrin receptor) returns from the early endosome to the cell surface, both directly and via recycling endosomes.
- 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. Hence, soluble molecules in the lumen of endosomes will tend to end up in lysosomes, unless they are retrieved in some way. Transmembrane proteinTransmembrane proteinA transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
s can be delivered to the perimeter membrane or the lumen of lysosomes. Transmembrane proteins destined for the lysosome lumen are sorted into the vesicles that bud from the perimeter membrane into endosomes, a process that begins in early endosomes. When the endosome has matured into a late endosome/MVB and fuses with a lysosome, the vesicles in the lumen are delivered to the lysosome lumen. Proteins are marked for this pathway by the addition of ubiquitinUbiquitinUbiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
. The endosomal sorting complexes required for transport (ESCRTESCRTESCRT refers to a series of cytosolic protein complexes called ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III.-Endocytosis and Receptor Down-Regulation:...
s) recognise this ubiquitin and sort the protein into the forming lumenal vesicles. Molecules that follow these pathways include LDL and the lysosomal hydrolases delivered by mannose-6-phosphate receptors. These soluble molecules remain in endosomes and are therefore delivered to lysosomes. Also, the transmembrane EGFRs, bound to EGF, are tagged with ubiquitin and are therefore sorted into lumenal vesicles by the ESCRTs.