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a-Catenin

updated 20/5/'02

a-catenin is an actin-binding protein at the adherens junction, that has overall similarity to vinculin, another actin-binding protein present at adhesional complexes.  It attaches the microfilaments ad associated proteins (vinculin, alpha-actinin) to the trans-membranous cell adhesion molecules (cadherins) via b-catenin.  In addition to being an important physical connection, this system is also important in cell signalling.  Free b-catenin is taken into the nucleus where it binds LEF-1 a transcription activator, this is the important Wnt pathway. b-catenin may also play a part in dendritic spines as it shuttles between the shafts and spines of neurons in a polarization sensitive manner (Murase et al, 2002).
 Figure 1.  a-catenin in relation to the other major components of the cell-cell adherent junction. This is a simplified diagram showing the major, but not all interconnections.
Protein Function Reference
actin A cytoskeletal component. Rimm et al, 1995
a-actinin An actin filament bundling protein Imamura et al, 1999
afadin A component of cell-cell adhesion complexes. Takahashi et al, 1999
b-catenin A signalling molecule that is also part of the adhesion complex Ozawa & Kemler, 1992
spectrin Usually present as part of the sub-membranous cytoskeleton where it connects various membranous proteins to actin. Pradham et al, 2001
vinculin A component of focal contacts and some cell adhesions that binds actin and lipids. Watabe-Uchida et al, 1998
ZO-1 A component of cell-cell adhesion complexes. Itoh et al, 1997
ZO-2 Binds ZO-1 is a MAGUK family member, present at tight and adherens junctions. Binds occludin. Itoh et al, 1999
Table 1 a-catenin-binding proteins
 

The structure of a-catenin
There are three regions of that are homologous to regions in vinculin (), 

The actin-binding site of a-catenin
It appears that the last 42 amino-acids of
a-catenin contains an actin-binding domain.  This is a bit odd because it was expected that the actin-binding domain would be contained within one of the regions that is homologous to vinculin as it too binds actin.  The last 42 amino-acids of a-catenin

a-catenin and disease
Mutations in
a-catenin genes are known to produce proteins that break the all important links between cell adhesion molecules and cell signalling throught through Wnt pathway (
Vanpoucke et al, 2002).  Disruption of adhesions releases b-catenin into the nucleus to switch on genes, while the broken cell adhesion leaves cells free to invade by locomotion.

References:- 

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Usui, T., Shima, Y., Shimada, Y., Hirano, S., Burgess, R. W., Schwartz, T. L., Takeichi, M. & Uemura, T. (1999) Flamingo, a seven-pass transmembrane cadherin, regulates planer cell polarity under the control of Frizzled. Cell. 98, 585-595.

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