18.6:
Maturation of Endosomes
Early endosomes transform into late endosomes through a process called the maturation of endosomes.
The early endosome moves from the periphery of a cell towards the perinuclear region. It first loses its tubular domains, and its vacuolar domain becomes roughly circular.
The endosomal membrane buds inwards to form numerous vesicles called intraluminal vesicles or ILVs. Hence, maturing endosomes are also known as multivesicular bodies or MVBs.
In addition, the trans-Golgi network delivers acid hydrolases and tethering proteins, such as SNAREs, to the maturing endosomes through vesicles.
V-type ATPases pump protons from the cytosol into the endosomal lumen, lowering the pH and activating the acid hydrolases.
Altogether, these changes are followed by the fusion of several endosomes with each other. The fusion increases the overall size and the number of intraluminal vesicles of the late endosome.
The late endosome then fuses with a lysosome to form an endolysosome. The acidic environment of the endolysosome helps maintain the activity of the acid hydrolases, which actively degrade the endocytosed ligand with the aid of lysosomal enzymes.
18.6:
Maturation of Endosomes
The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
Changes in location
The maturing endosome moves along microtubules from the periphery of the cell towards the perinuclear region. This movement of the endosome is mediated by dynein and kinesin motor proteins. Disruption of microtubules or inhibition of dynein leads to a delay in the maturation of endosomes or the dispersal of late endosomes.
Changes in intraluminal pH
The vacuolar domain of early endosomes contains V-type ATPases in its membrane. These enzymes pump protons from the cytosol into maturing endosomes. A lower intraluminal pH of the maturing endosome provides a better environment for the optimal functioning of the degradative enzymes in the maturing endosome and aids in efficient sorting of internalized molecules.
Changes in protein composition
Upon maturation, the late endosome is enriched with lysosomal hydrolases—proteins with degradative properties. Most of these hydrolases contain inhibitory domains that can inactivate their function. As the maturation progresses, these inhibitory domains are removed. Once the late endosome fuses with the lysosome, these hydrolases can degrade the endocytosed material. Additionally, the late endosome also acquires proteins called SNAREs, as well as some tethering proteins. SNAREs enable maturing endosomes to fuse with each other. Alternatively, they can later fuse with lysosomes and autophagosomes that are formed after phagocytosis.
Suggested Reading
- Huotari J. and Helenius A. Endosome Maturation. EMBO J (2011), 30(7): 3481-3500