What are Endosomes? Why are they present in a cell? Are they present in both animal and plant cells? How are they produced? Well, there are a myriad of questions like these. To be honest, Endosomes are not widely spoken on when we talk about cells and cell organelles. Despite not being given the attention they deserve, Endosomes play a very vital role in cellular function. Their absence can lead to disaster. In this article on Endosome facts, we are going to learn about these interesting compartments that allow our cells to perform optimally. However, in the process of understanding Endosomes, we are going to learn Endocytosis as well because it is important. Without learning Endocytosis, we cannot properly learn Endosomes. So, without further ado, let us begin…
Interesting Endosome Facts: 1-5 | Understanding Endocytosis
1. Endocytosis is a set or family of processes. These processes are very complex in nature. Endocytosis refers to the process of internalizing or taking in of material from outside the cell. In other words, materials that are outside the cell are taken inside the cell by this process. Remember that when we say cell, we are referring to eukaryotic cell (both plants and animals).
2. These eukaryotic cells are often known for internalizing various types of materials such as small and large molecules, different types of fluids and sometimes other cells. This internalization happens because it is necessary for various cellular processes including (but not limited to):
- Defence against microbes.
- Removal of damaged or dead cells from the body.
- Essential nutrients ingestion etc.
3. The process of Endocytosis is very important. What really happens during the process is that Plasma Membrane of the cell (remember that the Plasma Membrane is also known as Cell Membrane or Cytoplasmic Membrane) will fold inward. This process of folding inward is technically known as Invagination.
4. As the Plasma Membrane folds inwards, it creates a dent or pocket with two protruding arm-like structures extending outwards. These arm-like structures are called Pseudopodia (singular is Pseudopodium). As the extracellular material (material outside the cell) moves into the pit or pocket or dent the protruding arm-like structures will gradually go around the material and create an enclosed space.
5. These arm-like structures will then fuse together and completely enclose the material that gets into the pocket or pit or dent or compartment (whatever you prefer to call it). Once the foreign material is totally enclosed, that pocket or compartment will just pinch off from inner surface of the Plasma Membrane. This pinching off is known as Budding.
Interesting Endosome Facts: 6-10 | Understanding Endocytosis
6. The pinched-off compartment appears like a sac and is often known as a vesicle. This vesicle that pinches off the Plasma Membrane is then released into the Cytoplasm. The vesicle size may vary and only those vesicles that are bigger than 100 nm (nm means nanometer and one nanometer means one-billionth of a meter and in numeric terms it is written as 10-9 meters), the vesicle is known as Vacuole.
7. In our first point we said that Endocytosis is a set or family of processes. By that we mean to say that Endocytosis has different mechanisms. At least three different mechanisms have been identified so far. They are:
- Receptor Mediated Endocytosis
Let us take a look at each mechanism in brief.
8. Receptor Mediated Endocytosis: All active cells have receptor sites on their Cytoplasmic Membrane or Plasma Membrane. The receptors on these sites start from outer surface of the Plasma Membrane and extend all the way out into the extracellular fluid that surrounds each cell.
9. These receptor sites usually stay grouped together along certain pits of the Plasma Membrane. The specialty of these pits where these receptor sites are found is that the pits are coated from inside. The question is, “what kind of coating?”.
10. The coating is made of bristle-like proteins. These coat proteins are lined up on the inner surface of the Plasma Membrane.
Interesting Endosome Facts: 11-15 | Understanding Endocytosis
11. Specific types of molecules known as Ligands1 that come through the extracellular fluid are received by the receptors (which are also made of proteins) found on those receptor sites. When the Ligands are received by the receptors, they are moved into the coated pits.
12. Once inside the coated pits, the Pseudopodia fuse together to form a vesicle that then pinches off from the Plasma Membrane and get into the Cytoplasm. The vesicles that are formed from the coated pits are also coated vesicles. These coated vesicles not only contain the Ligands but also some receptors that may or may not be recycled back to the trans Plasma Membrane.
13. There are two things of note here. First, it is believed by scientists that the coat proteins play a major role in enlarging the pits that capture the Ligands. Second, though the coated pits majorly take in Ligands, they can also take in some molecules.
14. Pinocytosis (sometimes referred to as “Cell Drinking”): The process is pretty much the same as in case of Receptor Mediated Endocytosis except that there are no receptors near the pits and the pits are not coated. The pits here are responsible for taking in or internalizing liquid droplets from the extracellular fluid.
15. The solutes that are present in the liquid that is taken into the pits also get enclosed in the pits after the Pseudopodia close and fuse together. Once the fusing of the Pseudopodia takes place, the small sac-like vesicle simply pinches off the inner surface of the Plasma Membrane and move into the Cytoplasm.
Interesting Endosome Facts: 16-20 | Understanding Endocytosis
16. The vesicles that pinch off from the Plasma Membrane through the Pinocytosis mechanism are known as Pinocytic Vesicles and are the smallest of all vesicles formed by overall Endocytosis mechanisms.
17. The concentration of the solutes in the fluids encased in Pinocytic Vesicles is way higher than the concentration of those solutes in the extracellular fluid.
18. Phagocytosis (sometimes referred to as “Cell Eating”): Again, the process of vesicle formation is same as in case of Receptor Mediated Endocytosis and Pinocytosis. Also, in case of Phagocytosis, just like Pinocytosis, there are no receptors and no coated pits. Once the extracellular material enters a pit, the Pseudopodia close and fuse together by encircling the material and then, the compartment pinches off from the internal surface of the Plasma Membrane. The vesicle thus formed is large enough and almost the size of Vacuoles found in plant cells.
19. In Phagocytosis in multicellular animals, the purpose of engulfing extracellular material is for bodily defence and not for extraction of nutrition as in case of unicellular organisms. In unicellular organisms, an ameba for example, will extend out Pseudopodia to engulf food particles that are used for extracting nutrition.
20. In case of multicellular organisms, Phagocytosis is primarily meant for defence against attacking microbes. Foreign microbes are internalized through the mechanism of Phagocytosis. For instance, Leukocytes (one of the three blood cell type in humans) actually practice Phagocytosis to internalize bacteria, protozoa and other dead cells to prevent infections or other problems.
Now that we have learned about Endocytosis, we need to learn about Endosomes and find out their role in the cells. Let us start…
Interesting Endosome Facts: 21-25 | Endosome Facts and Functions
21. What are Endosomes? They are membrane-bound compartments that are present inside the eukaryotic cells. Their job is to provide an environment where the materials are sorted. So, they are sorting organelles within the eukaryotic cells.
22. Apart from sorting, Endosomes have at least two other functions. Those functions are:
- Trafficking of proteins and lipid vesicles to and from Plasma Membrane. This pathway is known as Endocytic Membrane Transport Pathway or Simply Endocytic Trafficking Pathway.
- Trafficking of proteins and lipid vesicles along the secretory pathway that involves the Endoplasmic Reticulum, Golgi Complex (including cis and trans Golgi Networks) and transport vesicles.
23. To make it simple, we can simply say that Endosomes are organelles that are known for working as stations for receiving and then delivering vesicles.
24. There are at least three different types of Endosomes that have been classified. The different types are:
- Early Endosomes
- Recycling Endosomes
- Late Endosomes or Multivesicular Endosomes (MVEs) or Multivesicular Bodies (MVBs)
25. As far as the shape of Endosomes is concerned, they are usually irregular in shape and look like large bags. However, there are times when they can actually form tubular structures.
Interesting Endosome Facts: 26-30 | Endosome Facts and Functions
26. Now comes endosomal organization. There are two popular theories trying to explain the organization of Endosomes inside eukaryotic cells. They are (REMEMBER THAT WE GAVE THESE NAME. THERE IS NO FORMAL RECOGNITION FOR THE NAMES):
- Type Model
- Maturation Model
27. Type Model of endosomal organization: This model states that the different types of Endosomes are already present inside a eukaryotic cell. The Early Endosomes are the ones that are located close to the Plasma Membrane or Cytoplasmic Membrane or Cell Membrane. They are the ones that are responsible for receiving vesicles from the Plasma Membrane.
28. Then there are Recycling Endosomes that are found deeper in the Cytoplasm and have the responsibility of delivering vesicles to the Plasma Membrane as well as the Golgi Body.
29. Finally there are Late Endosomes that are also known as Multivesicular Endosomes. These are the ones that receive hydrolytic enzymes-containing vesicles from the Golgi Body and are also responsible for sending back vesicles to Golgi Body for recycling.
30. These Late Endosomes eventually fuse with Lysosomes where the contents of the Late Endosomes are degraded by Lysosomes.
The Type Model says that these Endosomes are all stable compartments and they make use of vesicles for communicating with each other.
Interesting Endosome Facts: 31-35 | Endosome Facts and Functions
31. The Maturation Model is pretty different and is widely accepted. In this model it is hypothesized that endocytic vesicles fuse together forming Early Endosomes. These Early Endosomes are formed in the peripheral Cytoplasm of the Cell Membrane.
32. These Early Endosomes take some time for accumulating cargo. Around 8 minutes to 15 minutes are spent on this cargo accumulation. The molecules of the cargo are sorted into smaller vesicles that bud from the membrane of the Endosomes and are released into the lumen of the Endosomes. These vesicles are called intralumenal vesicles. It is during this cargo accumulation; the Early Endosomes also support the recycling of the Plasma Membrane through gradual acidification of the interior via Proton Pumps2. Plasma Membrane can be recycled by Early Endosomes either directly or by recycling the Endosomes located in perinuclear region.
33. Early Endosomes have several tubular regions. The gradual acidification of the interior of the Early Endosomes allows accumulation of molecules (that are to be recycled) to get concentrated in these tubular regions. These tubules then separate out and move into the recycling pathways. All this happens during the first 8 to 15 minutes.
34. Once that process is completed, the Early Endosomes start moving along Microtubules towards perinuclear space3, forming the nascent form of Late Endosomes (Note that the Late Endosomes are located in perinuclear region). Because the tubular structures of the Early Endosomes are lost during recycling, the nascent Late Endosomes are usually free of such tubular structures.
35. As the Early Endosomes start maturing into Late Endosomes, they will carry only a selected subset of cargo that was internalized by Endocytosis. This selected set of cargo is destined for degradation at Lysosomes.
Interesting Endosome Facts: 36-40 | Endosome Facts and Functions
36. As the nascent Late Endosomes continue moving along the microtubules, the selected cargo they inherit from Early Endosomes will mix with freshly synthesized Lysosomal Hydrolytic Enzymes (or Lysosomal Hydrolases) as well as membrane components that come through the secretory pathway (basically they come from the Golgi Body after being synthesized at Rough Endoplasmic Reticulum).
37. As the Late Endosomes keep moving along Microtubules4, they will fuse with each other through what is known as homotypic fusion reaction. Because of this fusion between Late Endosomes, they will grow in size and still, they will acquire more of intralumenal vesicles that come from the secretory pathway.
38. The already existing intralumenal vesicles and the newly acquired intralumenal vesicles give the Late Endosomes the appearance of Multivesicular Bodies or Multivesicular Endosomes.
39. Because the Late Endosomes are a part of the feeder system where they need to feed the endocytic cargo and the cargo from the secretory pathway to the Lysosomes for degradation, they need to prepare themselves for the encounter with Lysosomes. This is another stage of maturation in which they will lose one genetically coded marker protein called RAB5A and acquire another genetically coded marker protein called RAB7A. This newly acquired marker protein will allow the Late Endosomes to fuse with Lysosomes.
40. Once the fusion of a Late Endosome takes place with a Lysosome, a new transient organelle is produced. This is a hybrid organelle known as Endolysosome. It is in this Endolysosome that all the active degradation of the cargo takes place. After the degradation, another maturation stage follows in which the Endolysosome is converted into classical Lysosome which contains a dense brew of Lysosomal Hydrolases as well as membrane components.
The Maturation Model says that all the Endosomes are nothing but different stages of a single maturation process.
Interesting Endosome Facts: 41-45 | How Endosomes Work in Endocytic Trafficking Pathway
Before we start, we will like to say that we will use the Maturation Model for the purpose of explanation. Let’s begin…
In this image:
Phagosome: The cell takes in a bacterium using the Phagocytosis method of Endocytosis. As the bacterium is taken in it forms a vesicle containing the bacterium. This vesicle pinches off from the Plasma Membrane and forms a type of Endosome known as Phagosome. This Phagosome goes to the Lysosome to degrade the bacterium.
Endocytosis: The cell takes in extracellular material through endocytosis. The vesicle that separate out forms Early Endosome, which matures in Late Endosome and eventually fuses with Lysosome so that the Endocytosed material that is contained within the vesicle (Endosome) is degraded in the Lysosome).
Autophagy: Well, this is another type of cell activity where a defective cell organelle is sent to Lysosome. In this image the defective organelle is Mitochondiron. There are existing vesicles within the Cytosol of the cell. These vesicles will come together and surround the defective organelle by fusing with one another and form a compartment which is very similar to Endosome but the difference is that this compartment that surrounds the cell’s internal but defective organelle will have double membrane unlike single membrane of Endosome. This double membrane compartment containing the defective cell organelle is called Autophagosome and it is also destined for degradation in Lysosome.
41. The vesicles that are formed from Phagocytosis and Pinocytosis (sometimes known as Macropinocytosis) form special types of Endosomes known as Phagosomes and Macropinosomes respectively.
42. Phagosomes and Macropinosomes both follow the Endocytic Trafficking Pathway to eventually fuse with Lysosomes where the compartmentalized content or cargo of the Phagosomes and Macropinosomes are degraded by the hydrolytic enzymes present inside the Lysosomes.
43. The complexity comes when Endocytosis is receptor mediated Endocytosis. In this case, Clathrin-coated vesicles carrying endocytosed cargo is released into the Cytoplasm. Clathrin is a protein that coats the endocytic vesicles created by receptor mediated Endocytosis.
44. These Clathrin-coated vesicles contain the receptors that captured the Ligands from the extracellular space in the first place. However, the receptor-ligand interaction is highly sensitive to pH. Inside the Early Endosomes, the acidic conditions created by the Proton Pump by reduction of pH leads to separation of the receptors and Ligands. The receptors (which are transmembrane) will pile up in the tubular sections of the Early Endosomes.
45. These tubular sections will then bud off and return to the Plasma Membrane and fuse with it, releasing the receptors for reuse. The Ligands in the Early Endosome on other hand will stay as intralumenal vesicles. The Early Endosomes then move on to form Late Endosomes and finally fuse with Lysosomes in the process describe from points 31 to 40. There the degradation of the endocytosed cargo takes place.
Interesting Endosome Facts: 46-50 | How Endosomes Work in Secretory Pathway To Send Lysosomal Hydrolases to Lysosomes
46. The secretory pathway consists of the Endoplasmic Reticulum, the Golgi Complex (including cis Golgi Network or CGN and trans Golgi Network and TGN), transport vesicles, Cytosol etc. However, what we will study here is how Endosomes help in transporting Lysosomal Hydrolases to Lysosomes from Endoplasmic Reticulum.
In this image:
A Lysosomal Hydrolase precursor is synthesized in Rough Endoplasmic Reticulum and is added with a Mannose residue. The Lysosomal Hydrolase precursor along with the Mannose residue enters the cis Golgi Network and moves through the Golgi Apparatus. In the Golgi Body, Phospho-N-acetyl glucosamine (P-GlcNAc) is added to the Mannose residue.
The reason for this addition is that the Mannose residues are very hydrolytic and they can be cleaved easily. The Phospho-N-acetyl glucosamine (P-GlcNAc) prevents this from happening. Addition of Phospho-N-acetyl glucosamine actually adds a phosphate marker to the Lysosomal Hydrolase precursor in two steps.
First, Phospho-N-acetyl glucosamine is added to Mannose by a phosphotransferase. Second, a phosphodiesterase removes the sugar that was added to create a Mannose 6-Phosphate residue, which is actually a signal molecule. Once the signal molecule is attached to the Lysosomal Hydrolase, it moves to the trans Golgi Network where Mannose 6-Phosphate receptors wait.
Once in the trans Golgi Network, Clathrin proteins coat the budding vesicles. The adaptins present in Clathrin will then bind the Mannose 6-Phosphate receptors. These receptors in turn will bind the Lysosomal Hydrolase precursor with attached Mannose 6-Phosphate signal molecule. Once the binding is completed, the vesicle pinches off and moves towards the Early Endosome and fuses with it.
In Early Endosome, the pH levels are low (because of the Proton Pump pumping in Hydrogen ions from the Cytosol) and this forces the Mannose 6-Phosphate receptor to dissociate from Lysosomal Hydrolase. The empty receptor then goes in a budding vesicle from Early Endosome. The budding vesicle is then coated with another protein called “Retromer”. Once the coating is done, the vesicle containing the empty receptor pinches off and returns back to trans Golgi Network for reuse.
At the same time, the Lysosomal Hydrolase with Mannose 6-Phosphate residue is processed in the Early Endosome where the phosphate gets removed from the Mannose sugar which is attached to the Lysosomal Hydrolase. The removal of phosphate is essential because it ensures that the Hydrolase do not end up returning to Golgi Body along with the receptor. Once the phosphate is removed from the Lysosomal Hydrolase, it will fold properly and become activated. After the Early Endosome matures into Late Endosome and then fuses with Lysosome, the Lysosomal Hydrolase will become proper Lysosomal enzyme inside the Lysosome.
47. The Endoplasmic Reticulum is where Lysosomal Hydrolases or Lysosomal hydrolytic enzymes are manufactured. From the Endoplasmic Reticulum, transport vesicles carry the Lysosomal Hydrolases to the CGN. From CGN, the Hydrolases pass through the Golgi Complex and go through sorting and modification.
48. However, the Golgi Complex needs to identify the enzymes produced by Endoplasmic Reticulum as Lysosomal Hydrolases. To help the Golgi Apparatus, the Endoplasmic Reticulum tags the enzymes meant for Lysosomes with a specific type of molecule known as Mannose.
49. Once the Golgi processes the Lysosome-bound enzymes, they are sent to the TGN where M6P binding receptors wait. These receptors bind to the Lysosomal Hydrolases. Once the binding is completed, the cargo gets pinched off in a vesicle that is coated with Clathrin protein.
50. The pinched-off vesicles are released into the Cytoplasm and they move towards the Early Endosomes and fuse with the Early Endosome.
Interesting Endosome Facts: 51-55 | How Endosomes Work in Secretory Pathway To Send Lysosomal Hydrolases To Lysosomes
51. The Early Endosomes have acidic conditions inside them. This acidic condition is achieved using Proton Pumps that pump in positively charged Hydrogen ions from the Cytosol into the Early Endosomes thereby reducing their pH and increasing their acidity.
52. The acidic condition allows the M6P receptors to dissociate from the Lysosomal Hydrolases. Inside the Early Endosome, the phosphate of the M6P molecules attached to the Lysosomal Hydrolases are removed, leaving behind the activated Lysosomal Hydrolases.
53. On the other hand, the M6P receptors that get dissociated from the Lysosomal Hydrolases group together and move into the tubular sections of the Early Endosome, creating a budding vesicle. These budding vesicles then gets coated with another protein known Retromer protein.
54. Once the coating is completed, the vesicles containing the M6P receptors pinch off from the Early Endosome and move back to the trans Golgi Network or TGN where they are reused.
55. The Early Endosomes on the other hand then moves on to mature into Late Endosomes and finally fuse with Lysosomes where the Lysosomal Hydrolases are stored.
Ligands1: In cell biology, Ligands refer to small molecules that are known for transmitting signals within cells or between cells. Ligands bind to receptors (which are basically cellular proteins) to exert their effects.
Proton Pumps2: In cell biology, the proton pump is a transmembrane protein that can transport protons across Mitochondria, Cell Membrane or Plasma Membrane or other cell organelles.
Perinuclear Region3: It is the space that is between the inner and outer membranes that surround the nucleus of the cell. The space is about 20 to 40 nm wide.
Microtubules4: Most often found in eukaryotic cells, these are hollow shafts that are fibrous in nature. They are responsible for supporting a cell and giving it a shape. They are also known for providing support for transportation as they are the routes along which the cell organelles move inside a cell. Along with intermediate filaments and microfilaments, the microtubules for the cytoskeleton of a cell.
Some Endosome Facts (quick recap):
- Endosomes are vesicular organelle or vesicular compartments that are present in plant and animal cells.
- They are responsible for transporting materials that a cell ingests using a method called Endocytosis.
- They transport those material all the way up to Lysosomes.
- They also transport a few things produced inside a cell.
- Early Endosomes have a pH level of approximately 6.
- Late Endosomes have a pH level of approximately 5.5.
- The contents of Early Endosomes can go to Late Endosomes and then to Lysosomes. Or, those contents can be recycled all the way back to Plasma Membrane or they can the transferred between domains of polarized cells (this is something we will discuss later in a different article.
- Early Endosomes are located near the Plasma Membrane.
- Late Endosomes are located in perinuclear region.