αE-catenin, also known as Catenin alpha-1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''CTNNA1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. αE-catenin is highly expressed in

cardiac muscle Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...

and localizes to adherens junctions at intercalated disc structures where it functions to mediate the anchorage of

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

filaments to the

sarcolemma The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath), also called the myolemma, is the cell membrane surrounding a skeletal muscle fibre or a cardiomyocyte. It consists of a lipid bilayer and a thin ...

. αE-catenin also plays a role in tumor metastasis and skin cell function.

Structure

Human αE-catenin

is 100.0 kDa and 906

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s. Catenins (α,β,and γ (also known as plakoglobin)) were originally identified in complex with

E-cadherin Cadherin-1 or Epithelial cadherin (E-cadherin), is a protein that in humans is encoded by the ''CDH1'' gene (not to be confused with the APC/C activator protein CDH1). Mutations are correlated with Hereditary diffuse gastric cancer, gastric, Here ...

, an

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

cell adhesion

. αE-catenin is highly expressed in

and is homologous to the

vinculin; however, aside from vinculin, αE-catenin has no homology to established

-binding proteins. The

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

of αE-catenin binds β-catenin or γ-catenin/plakoglobin, and the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

binds

directly or indirectly via vinculin or α-actinin.

Function

Though αE-catenin exhibits substantial expression in

, αE-catenin is most well known for role in metastasizing tumor cells. αE-catenin also plays a role in

epithelial tissue Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

, both at adherens junctions and in signaling pathways. In cardiomyocytes, αE-catenin is present in cell to cell regions known as adherens junctions which lie within intercalated discs; these junctions anchor the actin

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

to the

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

resulting in a complete loss-of-function phenotype showed disruption of the

trophoblast The trophoblast (from Greek language, Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after Human fertilization, fertilization in humans. They provide nutrients to the embryo an ...

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

and arrested development at the

blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the ...

stage. αE-catenin specifically, not β- or γ-catenin, binds

F-actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

and organizes and tethers the filaments at regions of cell-cell contact. Studies show that full-length αE-catenin binds and bundles

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 N-cadherin that are involved in forming cell-cell contacts and differentiation of cardiomyocytes. Catenin-N-cadherin complexes are apparently necessary for and precede the first cell to cell contact, precursory to

gap junction Gap junctions are membrane channels between adjacent cells that allow the direct exchange of cytoplasmic substances, such small molecules, substrates, and metabolites. Gap junctions were first described as ''close appositions'' alongside tight ...

formation. The anchorage of cadherin-catenin complexes to actin filaments by αE-catenin is regulated by

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

. Functional insights into αE-catenin function have come from studies employing transgenesis. Mice harboring a cardiac-specific deletion of αE-catenin exhibited abnormalities in cardiac dimensions and function, representative of dilated cardiomyopathy. This was further characterized by disorganization of intercalated disc structures and

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

, as well as compensatory increases in β-catenin and decreases in localization of cadherin and vinculin at intercalated discs. Knockout mice also exhibited high susceptibility to death following stress.

Clinical significance

Interactions

αE-catenin has been shown to interact with: * APC, *

Beta-catenin Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcrip ...

, * CDH1, * CDH2, * CDH3 * Plakoglobin, and * VE-cadherin.

Structure

Function

Clinical significance

Interactions

See also

References

Further reading