Endosome

Endosomes are classified into three types: 1) Early endosomes, 2) late endosomes, and 3) recycling endosomes, depending on their stage post internalization and the presence of markers like Rabs. They are also morphologically different.

Endosomes participate in the process of endocytosis. The steps are as follows:

1. Cells engulf substances through the invagination of a portion of the plasma membrane, which is internalized, forming vesicles within the cell.
2. These vesicles then fuse with early endosomes, the sorting compartment of the pathway.
3. The early endosomes transform into late endosomes through maturation.
4. The substances taken up from late endosomes are either recycled to the plasma membrane or sent to lysosomes for degradation by recycling endosomes.

Endosomes also receive proteins and lipids synthesized from the rough endoplasmic reticulum and transfer them to the Golgi for sorting at the trans-Golgi network (TGN). This retrograde transport diverts proteins and lipids away from lysosomal degradation and helps in cell signaling.

Once the endocytic vesicles have been uncoated, they fuse with early endosomes, containing a tubular and a vacuolar domain. Late endosomes develop from early endosomes through maturation. These steps involve many modifications involving enzymes.

1. Early endosomes have specific protein and lipid composition that confers organelle identity. One such protein is Rab5, which regulates its morphology and functions. Rabs, the GTP-binding membrane proteins, switch between GTP-bound active and GDP-bound inactive states. A GTP-bound active Rab5 regulates the motility and binding of early endosomes with endocytic vesicles and activates several signaling pathways.
2. Rab5 localizes to the early endosomal membrane upon activation by Rabex5 and Rabaptin-5, exchange factors specific for Rab5. Apart from Rab5, some other markers found on early endosomes are phosphatidylinositol-3-phosphate (PtdIns-3-P) and endosome autoantigen 1 (EEA1).
3. The cell allows the recruitment of crucial Rab5 effectors such as PtdIns-3-P kinases, Vps34, and p150 to activate a positive feedback loop for Rab5. Finally, a switch in GTPases from Rab5 to Rab7 through the formation of transient Rab5/Rab7 hybrid marks early to late endosome maturation. SAND-1/Mon1 can dissociate Rabex-5 and Rabaptin-5 from the endosome membrane and allow association with Rab7. Other markers found on late endosomes are RAB9 and mannose 6-phosphate receptors.
4. Transport vesicles transfer substances targeted for lysosomal degradation from early to late endosomes. Those vesicles carry hydrolytic enzymes from the trans-Golgi network and fuse with late endosomes, causing the maturation of late endosomes into lysosomes.
5. Those substances that do not enter late endosomes recycle back to the plasma membrane with the help of transport vesicles named recycling endosomes. The recycling endosomes develop from the early sorting endosome and are found at the microtubule organizing center. They have marker Rab11 on their surface.
6. The vesicles, on reaching the plasma membrane, fuse and then bud off, similar to the process of endocytosis.

Endosome plays some vital roles during the functioning of the cell:

1. Regulating Cell Surface Receptors

Upon binding to the ligand, the extracellular domain of the transmembrane receptor enters the endosomal pathway. The ligand-receptor complex is assembled on specific clathrin-coated sites of the plasma membrane. These regions invaginate and engulf the receptor-ligand complex, which then buds off the plasma membrane to form clathrin-coated vesicles (clathrin-mediated endocytosis).

The clathrin-coated vesicles fuse with early endosomes, where the internalized receptor-ligand complex is sorted. The endosome-mediated degradation of the internalized substance marks the end of the receptor-mediated signaling event. Recycling the receptor to the plasma membrane causes the pathway to continue.

2. Uptake of Nutrients

The cell also takes up nutrients following the same process of receptor-mediated endocytosis. The cholesterol uptake occurs through the low-density lipoprotein (LDL) receptor in the clathrin-coated sites of the plasma membrane.

The LDL receptor detaches from its ligand during internalization and fusion to early endosomes. It is recycled back to the plasma membrane. The LDL moves towards lysosomes, where they fuse, leading to the degradation of LDL and the release of cholesterol for cellular use.

3. Clathrin-Independent Endocytosis

Other than clathrin-mediated endocytosis, some membrane proteins and extracellular fluids internalize through specific vesicles called caveolae. These vesicles are made of caveolin protein and are internalized and sorted following the same process as receptor-mediated endocytosis.

4. Transmission of Nerve Impulse

During transmission of a nerve impulse and upon generation of the action potential, presynaptic vesicles fuse with the plasma membrane, releasing neurotransmitters and transmitting signals to the postsynaptic neurons.

The postsynaptic vesicles are then removed from the plasma membrane through endocytosis, which is then taken up by the endosomes. Within the endosome, regeneration of the synaptic vesicle takes place. Finally, newly formed synaptic vesicles containing neurotransmitters are recycled back to the plasma membrane.

Abnormality in the endosomes is known to cause some health complications.

In patients with high blood cholesterol, the LDL receptor has two mutations and thus cannot perform endocytosis. One of the mutations prevents the binding of LDL with its receptor, and the other stops the accumulation of LDL receptors in the clathrin-coated pits. Thus, the receptor complex cannot be internalized for processing.

In patients who have Alzheimer’s disease, endosomal dysfunction is associated with neurodegenerative disorders.

Differences

The key differences between an endosome and a lysosome are as follows:

Similarities

Both are:

• Membrane-bound vesicles
• Involved in cell functioning
• Produced from Golgi apparatus
• Involved in endocytosis