Scientists know that cells in all higher organisms cells need to bind to each other for the development, architecture, maintenance and function of tissues. Mysteries have remained, however, about exactly how cells manage this feat.
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have now solved part of this puzzle by defining the structure of a protein known as α-catenin, which is essential to this process.
The work was published online ahead of print on January 6, 2012, by the journal Nature Structural & Molecular Biology.
Chain, Chain, Chain
Our cells bind to each other using specialized cell surface adhesion complexes called adherens junctions, which direct the formation of tight, Velcro-like contacts among cells.
Adherens junctions are made up of three types of proteins—cadherin, α-catenin and β-catenin. First, cadherin receptors, which span the cell membrane, direct the binding of cells to each other using domains that project outside the cell. Second, their tail domains, found on the inside of the cell, bind to the protein β-catenin, which, in turn, is bound to α-catenin.
The term catenin is derived from the Latin word for chain, catena, and these three proteins literally make a chain. This complex is then stabilized when the end of the chain, α-catenin, attaches to the molecular framework of the cell, the cytoskeleton. Without this, link cells would simply be amorphous piles of goo. Furthermore, alterations of cadherins, β-catenin and/or α-catenin can lead to marked changes in cell signaling, growth and migration—which can result in abnormalities and cancer.
Confronting a Paradox
Exactly how α-catenin provides links to the cytoskeleton and to the cadherin-β-catenin complex, however, has long puzzled scientists.
Scientists have known that α-catenin forms links to the cytoskeleton by binding to a protein called F-actin (the "F" stands for filament), which is found in species ranging from yeast to humans. The paradox for scientists has been that, despite being able to bind to F-actin on its own, when bound to α-catenin α-catenin cannot bind to F-actin. That is, the binding of α-catenin to F-actin and to β-catenin are, in the test tube, mutually exclusive. So how does α-catenin bind to F-actin versus β-catenin and how is the final link in the chain stabilized in cells?
To resolve this paradox, the scientists crystallized and determined the structure of a nearly full-length human α-catenin. This structure showed why α-catenin cannot simultaneously bind to F-actin and β-catenin. Specifically, in its unbound state, α-catenin was shown to be an asymmetric dimer, where the two subunits have remarkable differences in their architecture that appear to together create the binding site for F-actin. Binding of β-catenin to α-catenin disrupts the interaction of its two subunits, changing its architecture and displacing F-actin.
The second part of the puzzle—how cadherin-β-catenin and α-catenin-F-actin complexes are linked together in cells—was resolved when the scientists realized that another cytoskeleton protein called vinculin, which can also bind to F-actin, plays a critical role in this process. The scientists established the structures of dimeric α-catenin alone and when in complex with pre-activated vinculin. The results showed that vinculin binding did not disrupt the α-catenin dimer and that both partners of the vinculin-α-catenin complex were in fact capable of binding to F-actin, a scenario that stabilizes adhesion complexes.
Scripps Research Institute: http://www.scripps.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
A riverside in Nebraska is a welcome refuelling stop for these elegant birds migrating from Mexico to their breeding grounds
Deprived of sight, blind people manage to squeeze an amazing amount of information out of their other senses. Doing this requires their brains to do some reorganizing. To learn about some of these changes, scientists studied the brains of blind people ...
In 1973, American soldiers on the Mekong River in Laos killed and hauled ashore a massive 24-foot ribbon of a fish. It was the “Queen of the Naga,” claimed a postcard still widely circulated in Southeast Asia with the above ...
Bald eagles have made a comeback. See life in the nest now during peak nesting season.
Photos capture a river otter attacking a gator in a Florida river. The otter then feasted, witnesses say.
The 10-meter long Torvosaurus weighed up to five tons.
Researchers say the key to fighting superbugs is individualized treatment plans, and a new nanochip might pave the way
Some farmers have long sworn by mellow tunes to boost Bessie's milk production. The science is hardly conclusive. But a study hints at what might top the barnyard playlist. (Psst: They liked R.E.M.)
Craig Venter, the U.S. scientist who raced the U.S. government to map the human genome over a decade ago and created synthetic life in 2010, is now on a quest to treat age-related disease.
Dr Dave Hone: The Daohugou Fauna is rich in dinosaurs, lizards, pterosaurs, salamanders and mammalsDr Dave Hone