Scientists from Cornell University have gained new insight into how receptors on cell surfaces turn off signals from their environment. Their results may have a great influence on the understanding of cancer, AIDS, neurodegenerative disorders, and other illnesses.
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The cell surface holds a wide variety of receptors, composed of proteins. These receptors control the interactions between cells and their environment. Using these receptors, cells receive signals telling them to undergo mitosis, start inner processes, activate certain genes, and even undergo apoptosis (cell death). Clearly, to make sure the cell functions properly, the type, amount, and activation of receptors on the surface must be closely regulated. Many diseases, such as AIDS, may result from cells’ inabilities to down-regulate the activity of its receptors.
The machinery responsible for down regulation of receptors is called ESCRT (for endosomal sorting complex required for transport). The ESCRT packages receptors into multivesicular bodies (MVBs), temporary transport structures that control the down-regulation and the degradation of receptors. MVBs are clusters of small vesicles surrounded by a limiting membrane that occurs in a cell’s cytoplasm. They are critical for a variety of cellular functions ranging from lysosomal degradation to the budding of HIV.
Working with Scott Emr, director of Cornell’s Weill Institute for Cell and Molecular Biology and professor of molecular biology and genetics, the researchers used bakers yeast as an animal model and discovered the mechanism by which the ESCRT machinery directs the formation of the MVB transport structure.
Common intercellular transport reactions, such as secreted insulin delivery to the cell surface, work through the formation of small membrane vesicles that bud into the cytoplasm of the cell. MVB is different. The MVB membrane compartment holds within it membrane vesicles that form by budding out of the cytoplasm and into the MVB. Erm’s team discovered that the ESCRT machinery is responsible for the deformation of cell membrane that generates these internal vesicles.
“The ESCRT machinery catalyzes a transport reaction that is topologically opposite to most other intercellular transport reactions in the cell,” said Emr.
Additional findings suggest that the machinery assembles by forming a ring-like filament that contains receptors that will end up packaged in the MVBs. “This ESCRT ring also serves as a scaffold to direct the topology of membrane deformation,” Emr said. Viruses like HIV use the ESCRT ring to deform the cell membrane and bud out of the cell, thus forming the free virus that can then infect healthy cells in AIDS patients.
“Diverse biological processes – MVB formation, cell division and viral budding – share the same budding topology,” Emr explained. “Interestingly, these seemingly unrelated processes all require the function of the ESCRT machinery.”
The understanding of the ESCRT machinery’s role in diseases such as AIDS will move the scientific world forward towards a deeper understanding of the disease mechanisms. Further research of ESCRT proteins may help in the development of drugs for the treatment of AIDS, neurodegenerative disorders, and more.
Receptors play a great part in the cell function and TFOT has brought you several stories involving receptors. One such story described a technique of filtering cancer cells out of the blood using special cancer receptors, also developed at Cornell University. Another story described the TRAIL receptor, which connects cancer and inflammation, and was discovered by a research team at the University of Pennsylvania School of Medicinee.
For more information on the protein receptors research visit the Cornell news page.
