18.10:
Recycling Endosomes and Transcytosis
Macromolecules endocytosed from the plasma membrane follow three pathways to different fates. They can be degraded upon fusion with a lysosome, recycled back to the same domain of the plasma membrane, or transported to a different domain of the plasma membrane.
Molecules destined to be transported across the cell to another plasma membrane domain are internalized in vesicles that fuse with the recycling endosome.
The recycling endosome is a tubulated membrane network that acts as an intermediate structure to store and transport endocytosed molecules.
Transcytosis is one way to transport molecules across the plasma membrane through the recycling endosomes. This process has three distinct steps—endocytosis, vesicular transfer, and exocytosis.
18.10:
Recycling Endosomes and Transcytosis
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across the cell to a different plasma membrane domain. Recycling endosomes also play a crucial role in maintaining the required concentration of plasma membrane proteins. For example, recycling endosomes store glucose transporters in fat and muscle cells until insulin stimulates these vesicles to fuse with the plasma membrane. This brings the glucose transporters to the surface so that glucose may enter the cell.
The endocytic recycling process is regulated by the Rab11 subfamily of proteins and other Rab GTPases. The Rab11 subfamily proteins recruit effectors such as the Rab11 family of interacting proteins (Rab11-FIPs) to distinct domains of the ERC. In addition to FIPs, Rab11 also recruits motor proteins such as kinesin, dynein, and myosin to the ERC to recycle specific molecules to the plasma membrane.
The endosomal recycling pathway is reported to be hijacked by some viral and bacterial pathogens. These pathogenic viral particles fuse with Rab11-positive recycling endosomes before uncoating in the cytoplasm. Similarly, pathogenic bacteria, such as Shigella or Salmonella inject effector proteins into cells under regulation by Rab11. These effector proteins rearrange the cytoskeleton to form a vacuole around the pathogen. The vacuole inhibits the endolysosome from degrading the pathogen. Thus, interference with the endosomal recycling pathway or perturbation of Rab 11 can be used to treat specific viral or bacterial infections.
Suggested Reading
- Goldenring, J. R. (2015). Recycling endosomes. Current opinion in cell biology, 35, 117-122.
- O'Sullivan, M. J., & Lindsay, A. J. (2020). The Endosomal Recycling Pathway—At the Crossroads of the Cell. International Journal of Molecular Sciences, 21(17), 6074.
- Tuma, P. L., & Hubbard, A. L. (2003). Transcytosis: crossing cellular barriers. Physiological reviews, 83(3), 871-932.