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α-catenin: at the junction of intercellular adhesion and actin dynamics

Nature Reviews Molecular Cell Biology volume 5, pages 614–625 (2004)Cite this article

Key Points

  • The α-catenin family consists of four members — αE-catenin, αN-catenin, αT-catenin and α-catulin — all of which seem to have important functions in development and differentiation.

  • Several interesting insights regarding α-catenin function have been gained from structural studies of the α-catenin M-fragment, dimerization and β-catenin-binding domains, as well as comparisons with vinculin structure.

  • α-catenin seems to be a central component in nucleating the assembly of a multiprotein complex that links E-cadherin–β-catenin complexes to F-actin. This is important for stabilizing adherens junctions, sealing membranes and assembling epithelial sheets. Several proteins link α-catenin to the actin cytoskeleton.

  • The dynamic remodelling of adhesive contacts is required for the maintenance of organized epithelia, so binding of α-catenin to the E-cadherin–β-catenin complex has to be tightly regulated.

  • The disruption of cadherin-based adhesion has a central role in the progression of human epithelial cancers. Reduced levels of E-cadherin and α-catenin proteins have been reported as a characteristic of many different human cancers.

  • α-catenin interacts with proteins, such as Ajuba, which might link adhesion and signalling in the nucleus.

Abstract

α-catenin has often been considered to be a non-regulatory intercellular adhesion protein, in contrast to β-catenin, which has well-documented dual roles in cell–cell adhesion and signal transduction. Recently, however, α-catenin has been found to be important not only in connecting the E-cadherin–β-catenin complex to the actin cytoskeleton, but also in coordinating actin dynamics and inversely correlating cell adhesion with proliferation. As the number of α-catenin-interacting partners increases, intriguing new connections imply even more complex regulatory functions for this protein.

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Figure 1: Intercellular junctions in skin.
Figure 2: A multiprotein complex at adherens junctions.
Figure 3: Abnormal cerebellar development in αN-catenin-mutant mice.
Figure 4: Sequence similarities between vinculin and αE-catenin.
Figure 5: Comparison of the crystal structures of the αE-catenin M-fragment and vinculin tail.
Figure 6: Functionally important regions of αE-catenin.
Figure 7: Model of adherens-junction formation in keratinocytes.

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Acknowledgements

We are grateful to D. Barford and D. R. Critchley for providing us with images. E.F. is an investigator at the Howard Hughes Medical Institute, New York, USA. A.K. is a research associate supported by the US National Institutes of Health.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, Rockefeller University, 1230 York Avenue, Box 300, New York, 10021, New York, USA

    Agnieszka Kobielak & Elaine Fuchs

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  1. Agnieszka Kobielak
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  2. Elaine Fuchs
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Correspondence to Elaine Fuchs.

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DATABASES

Entrez Gene

CTNNA1

CTNNA2

CTNNA3

CTNNAL1

Fmn1

Grem1

Swiss-Prot

Ajuba

Armadillo

β-catenin

α-catulin

desmoplakin

DIA1

E-cadherin

αE-catenin

FGF4

FMN1

gremlin

HMP-1

HMP-2

HMR-1

IQGAP1

LEF1

myosin VIIA

αN-catenin

p120 catenin

plakoglobin

SHH

VASP

vezatin

vinculin

ZO1

Glossary

CLASSIC CADHERINS

Cadherins are transmembrane molecules that mediate Ca2+-dependent cell–cell adhesion. Classic cadherins are typified by an extracellular segment that consists of five distinct Ca2+-binding domains and a conserved cytoplasmic domain, which binds β-catenin. The extracellular part interacts homotypically with cadherins on the surface of neighbouring cells to form adherens junctions. The cytoplasmic tail links the actin cytoskeleton to adherens junctions.

ADHERENS JUNCTION

A specialized intercellular junction of the plasma membrane, in which the cadherin molecules of adjacent cells interact in a Ca2+-dependent manner. Actin filaments are linked to this structure through catenins that are located underneath the junction.

DESMOSOMES

Specialized junctional structures that form a tight connection between epithelial cells or cardiac myocytes. They consist of several transmembrane adhesive glycoproteins (desmogleins and desmocollins) and cytoplasmic plaque proteins (desmoplakins) that link to intermediate filaments.

INTERMEDIATE FILAMENTS

Proteins that acquired their name from the diameter of their polymeric structure, which is midway between the diameters of thin actin microfilaments and thick microtubules. Their ability to form very stable filaments enables them to confer mechanical strength on the cytoskeleton.

ACTOMYOSIN NETWORK

A complex of myosin and actin filaments that is responsible for a range of cellular movements in eukaryotic cells. Myosins can translocate vesicles or other cargo on actin filaments.

TIGHT JUNCTIONS

The most apical intercellular junctions, which function as selective (semi-permeable) diffusion barriers between individual cells. They are identified as a belt-like region in which two lipid-apposing membranes lie close together.

FOCAL ADHESIONS

A cell-to-substrate adhesion structure that anchors the ends of actin microfilaments (stress fibres) and mediates strong attachment to substrates.

GENE TRAP

A methodology that is used to characterize new genes and analyse their importance in biological phenomena. The technique involves the use of mouse embryonic stem cells and reporter vectors that are designed to randomly integrate into the genome, tag an insertion site and generate a mutation.

BLASTOCYST STAGE

The stage during embryonic development that is characterized by the formation of two cell types: the embryoblast (the inner cell mass on the inside of the blastocoel) and the trophoblast (the cells on the outside of the blastocoel).

ACTIVE ZONES

The sites along nerve terminals where synaptic vesicles dock and undergo Ca2+-dependent exocytosis during synaptic transmission.

PURKINJE CELLS

Large neurons with extensive dendritic projections that form a layer near to the surface of the cerebellum.

DILATED CARDIOMYOPATHY

Also known as 'congestive cardiomyopathy', this is the most common form of myocardial disease, which causes decreased systolic function and increased ventricular volume.

AMPHIPATHIC HELICES

Helical structures that consist of hydrophobic non-polar residues on one side of the helical cylinder, and hydrophilic and polar residues on the other side.

YEAST TWO-HYBRID ANALYSIS

A technique that is used to study protein–protein interactions in vivo in yeast cells.

GUANINE NUCLEOTIDE-EXCHANGE FACTOR

A protein that facilitates the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) in the nucleotide-binding pocket of a GTP-binding protein.

L CELLS

Cells of a mouse fibroblast line that is derived from connective tissue and does not express classic cadherin molecules.

KERATINOCYTES

Differentiated epithelial cells of the skin.

BARBED END

The fast-polymerizing end of an actin filament, which is defined by the arrowhead-shaped decoration of actin filaments with myosin fragments.

FORMIN FAMILY

A family of multidomain scaffold proteins that are involved in actin-dependent morphogenetic events. They are conserved from fungi to humans and are characterized by the presence of two conserved carboxy-terminal regions: the formin homology (FH) domains FH1 and FH2.

FILOPODIA

Thin, transient actin protrusions that extend out from the cell surface and are formed by the elongation of bundled actin filaments in its core.

LAMELLIPODIA

Cellular protrusions that contain extensively branched arrays of actin filaments, which are orientated with their plus (barbed) ends toward the plasma membrane.

Arp2/3 PROTEIN COMPLEX

A complex that consists of two actin-related proteins, Arp2 and Arp3, along with five smaller proteins. When activated, the Arp2/3 complex binds to the side of an existing actin filament and nucleates the assembly of a new actin filament. The resulting branch structure is Y-shaped.

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Kobielak, A., Fuchs, E. α-catenin: at the junction of intercellular adhesion and actin dynamics. Nat Rev Mol Cell Biol 5, 614–625 (2004). https://doi.org/10.1038/nrm1433

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