Catenin alpha-1

αE-catenin, also known as Catenin alpha-1 is a is_associated_with::protein that in humans is encoded by the CTNNA1 is_associated_with::gene. αE-catenin is highly expressed in is_associated_with::cardiac muscle and localizes to is_associated_with::adherens junctions at is_associated_with::intercalated disc structures where it functions to mediate the anchorage of actin filaments to the is_associated_with::sarcolemma. αE-catenin also plays a role in tumor metastasis and skin cell function.

Structure
Human αE-catenin is_associated_with::protein is 100.0 kDa and 906 is_associated_with::amino acids. Catenins (α,β,and γ (also known as is_associated_with::plakoglobin)) were originally identified in complex with is_associated_with::E-cadherin, an epithelial cell adhesion is_associated_with::protein. αE-catenin is highly expressed in is_associated_with::cardiac muscle and is homologous to the is_associated_with::protein is_associated_with::vinculin; however, aside from is_associated_with::vinculin, αE-catenin has no homology to established actin-binding proteins. The is_associated_with::N-terminus of αE-catenin binds β-catenin or γ-catenin/plakoglobin, and the is_associated_with::C-terminus binds actin directly or indirectly via is_associated_with::vinculin or α-actinin.

Function
Though αE-catenin exhibits substantial expression in is_associated_with::cardiac muscle, αE-catenin is most well known for role in metastasizing tumor cells. αE-catenin also plays a role in epithelial tissue, both at is_associated_with::adherens junctions and in signaling pathways.

In is_associated_with::cardiomyocytes, αE-catenin is present in cell to cell regions known as is_associated_with::adherens junctions which lie within is_associated_with::intercalated discs; these junctions anchor the actin is_associated_with::cytoskeleton to the is_associated_with::sarcolemma and provide strong cell adhesion.

Functional αE-catenin is required for normal embryonic development, as a mutation eliminating the C-terminal 1/3 of the is_associated_with::protein resulting in a complete loss-of-function phenotype showed disruption of the is_associated_with::trophoblast is_associated_with::epithelium and arrested development at the is_associated_with::blastocyst stage.

αE-catenin specifically, not β- or γ-catenin, binds F-actin and organizes and tethers the filaments at regions of cell-cell contact. Studies show that full-length αE-catenin binds and bundles F-actin in a superior fashion relative to individual N-terminal or C-terminal domains.

αE-catenin, along with β-catenin and plakoglobin form distinct complexes with is_associated_with::N-cadherin that are involved in forming cell-cell contacts and differentiation of is_associated_with::cardiomyocytes. Catenin-N-cadherin complexes are apparently necessary for and precede the first cell to cell contact, precursory to is_associated_with::gap junction formation. The anchorage of cadherin-catenin complexes to actin filaments by αE-catenin is regulated by is_associated_with::tyrosine is_associated_with::phosphorylation.

Functional insights into αE-catenin function have come from studies employing transgenesis. Mice harboring a is_associated_with::cardiac-specific deletion of αE-catenin exhibited abnormalities in cardiac dimensions and function, representative of is_associated_with::dilated cardiomyopathy. This was further characterized by disorganization of is_associated_with::intercalated disc structures and is_associated_with::mitochondria, as well as compensatory increases in β-catenin and decreases in localization of cadherin and vinculin at is_associated_with::intercalated discs. Knockout mice also exhibited high susceptibility to death following stress.

Interactions
αE-catenin has been shown to interact with:


 * APC,
 * is_associated_with::Beta-catenin,
 * CDH1,
 * is_associated_with::CDH2,
 * CDH3
 * is_associated_with::Plakoglobin,  and
 * is_associated_with::VE-cadherin.