αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the CTNNA1 gene.[5][6] αE-catenin is highly expressed in cardiac muscle and localizes to adherens junctions at intercalated disc structures where it functions to mediate the anchorage of actin filaments to the sarcolemma. αE-catenin also plays a role in tumor metastasis and skin cell function.
Structure
editHuman αE-catenin protein is 100.0 kDa and 906 amino acids.[7] Catenins (α,β,and γ (also known as plakoglobin)) were originally identified in complex with E-cadherin, an epithelial cell adhesion protein. αE-catenin is highly expressed in cardiac muscle[8][9] and is homologous to the protein vinculin; however, aside from vinculin, αE-catenin has no homology to established actin-binding proteins. The N-terminus of αE-catenin binds β-catenin or γ-catenin/plakoglobin, and the C-terminus binds actin directly or indirectly via vinculin or α-actinin.[10]
Function
editThough αE-catenin exhibits substantial expression in cardiac muscle, αE-catenin is most well known for role in metastasizing tumor cells.[11] αE-catenin also plays a role in epithelial tissue, both at adherens junctions and in signaling pathways.[12]
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 to the sarcolemma and provide strong cell adhesion.[13]
Functional αE-catenin is required for normal embryonic development, as a mutation eliminating the C-terminal 1/3 of the protein resulting in a complete loss-of-function phenotype showed disruption of the trophoblast epithelium and arrested development at the blastocyst stage.[14]
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.[15]
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 formation.[16] The anchorage of cadherin-catenin complexes to actin filaments by αE-catenin is regulated by tyrosine phosphorylation.[17]
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, 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.[18]
Clinical significance
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Interactions
editαE-catenin has been shown to interact with:
See also
editReferences
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- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037815 – Ensembl, May 2017
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- ^ "Entrez Gene: CTNNA1 catenin (cadherin-associated protein), alpha 1, 102kDa".
- ^ "Protein sequence of human CTNNA1 (Uniprot ID: P35221)". Cardiac Organellar Protein Atlas Knolwedgebase (COPaKB). Archived from the original on 4 July 2015. Retrieved 3 July 2015.
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- ^ Rimm DL, Koslov ER, Kebriaei P, Cianci CD, Morrow JS (Sep 1995). "Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex". Proceedings of the National Academy of Sciences of the United States of America. 92 (19): 8813–7. Bibcode:1995PNAS...92.8813R. doi:10.1073/pnas.92.19.8813. PMC 41057. PMID 7568023.
- ^ Hertig CM, Butz S, Koch S, Eppenberger-Eberhardt M, Kemler R, Eppenberger HM (Jan 1996). "N-cadherin in adult rat cardiomyocytes in culture. II. Spatio-temporal appearance of proteins involved in cell-cell contact and communication. Formation of two distinct N-cadherin/catenin complexes". Journal of Cell Science. 109 (1): 11–20. doi:10.1242/jcs.109.1.11. PMID 8834786.
- ^ Aberle H, Schwartz H, Kemler R (Jun 1996). "Cadherin-catenin complex: protein interactions and their implications for cadherin function". Journal of Cellular Biochemistry. 61 (4): 514–23. doi:10.1002/(SICI)1097-4644(19960616)61:4<514::AID-JCB4>3.0.CO;2-R. PMID 8806074. S2CID 24566745.
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- ^ Su LK, Vogelstein B, Kinzler KW (December 1993). "Association of the APC tumor suppressor protein with catenins". Science. 262 (5140): 1734–7. Bibcode:1993Sci...262.1734S. doi:10.1126/science.8259519. PMID 8259519.
- ^ Daniel JM, Reynolds AB (September 1995). "The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin". Mol. Cell. Biol. 15 (9): 4819–24. doi:10.1128/mcb.15.9.4819. PMC 230726. PMID 7651399.
- ^ Oyama T, Kanai Y, Ochiai A, Akimoto S, Oda T, Yanagihara K, Nagafuchi A, Tsukita S, Shibamoto S, Ito F (December 1994). "A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines". Cancer Res. 54 (23): 6282–7. PMID 7954478.
- ^ a b Roe S, Koslov ER, Rimm DL (June 1998). "A mutation in alpha-catenin disrupts adhesion in clone A cells without perturbing its actin and beta-catenin binding activity". Cell Adhes. Commun. 5 (4): 283–96. doi:10.3109/15419069809040298. PMID 9762469.
- ^ Piedra J, Miravet S, Castaño J, Pálmer HG, Heisterkamp N, García de Herreros A, Duñach M (April 2003). "p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction". Mol. Cell. Biol. 23 (7): 2287–97. doi:10.1128/mcb.23.7.2287-2297.2003. PMC 150740. PMID 12640114.
- ^ Aberle H, Butz S, Stappert J, Weissig H, Kemler R, Hoschuetzky H (December 1994). "Assembly of the cadherin-catenin complex in vitro with recombinant proteins". J. Cell Sci. 107 (12): 3655–63. doi:10.1242/jcs.107.12.3655. PMID 7706414.
- ^ Reuver SM, Garner CC (April 1998). "E-cadherin mediated cell adhesion recruits SAP97 into the cortical cytoskeleton". J. Cell Sci. 111 (8): 1071–80. doi:10.1242/jcs.111.8.1071. PMID 9512503.
- ^ Kinch MS, Clark GJ, Der CJ, Burridge K (July 1995). "Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia". J. Cell Biol. 130 (2): 461–71. doi:10.1083/jcb.130.2.461. PMC 2199929. PMID 7542250.
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- ^ Lewalle JM, Bajou K, Desreux J, Mareel M, Dejana E, Noël A, Foidart JM (December 1997). "Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro". Exp. Cell Res. 237 (2): 347–56. doi:10.1006/excr.1997.3799. hdl:2268/61990. PMID 9434630.
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Further reading
edit- Nagafuchi A, Takeichi M, Tsukita S (1991). "The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression". Cell. 65 (5): 849–57. doi:10.1016/0092-8674(91)90392-C. PMID 1904011. S2CID 38622586.
- Kinch MS, Clark GJ, Der CJ, Burridge K (1995). "Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia". J. Cell Biol. 130 (2): 461–71. doi:10.1083/jcb.130.2.461. PMC 2199929. PMID 7542250.
- Sacco PA, McGranahan TM, Wheelock MJ, Johnson KR (1995). "Identification of plakoglobin domains required for association with N-cadherin and alpha-catenin". J. Biol. Chem. 270 (34): 20201–6. doi:10.1074/jbc.270.34.20201. PMID 7650039.
- Daniel JM, Reynolds AB (1995). "The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin". Mol. Cell. Biol. 15 (9): 4819–24. doi:10.1128/mcb.15.9.4819. PMC 230726. PMID 7651399.
- Aberle H, Butz S, Stappert J, Weissig H, Kemler R, Hoschuetzky H (1995). "Assembly of the cadherin-catenin complex in vitro with recombinant proteins". J. Cell Sci. 107 (12): 3655–63. doi:10.1242/jcs.107.12.3655. PMID 7706414.
- Knudsen KA, Soler AP, Johnson KR, Wheelock MJ (1995). "Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin". J. Cell Biol. 130 (1): 67–77. doi:10.1083/jcb.130.1.67. PMC 2120515. PMID 7790378.
- Rimm DL, Kebriaei P, Morrow JS (1994). "Molecular cloning reveals alternative splice forms of human alpha(E)-catenin". Biochem. Biophys. Res. Commun. 203 (3): 1691–9. doi:10.1006/bbrc.1994.2381. PMID 7945318.
- Oyama T, Kanai Y, Ochiai A, Akimoto S, Oda T, Yanagihara K, Nagafuchi A, Tsukita S, Shibamoto S, Ito F (1994). "A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines". Cancer Res. 54 (23): 6282–7. PMID 7954478.
- McPherson JD, Morton RA, Ewing CM, Wasmuth JJ, Overhauser J, Nagafuchi A, Tsukita S, Isaacs WB (1994). "Assignment of the human alpha-catenin gene (CTNNA1) to chromosome 5q21-q22". Genomics. 19 (1): 188–90. doi:10.1006/geno.1994.1042. PMID 8188230.
- Su LK, Vogelstein B, Kinzler KW (1994). "Association of the APC tumor suppressor protein with catenins". Science. 262 (5140): 1734–7. Bibcode:1993Sci...262.1734S. doi:10.1126/science.8259519. PMID 8259519.
- Oda T, Kanai Y, Shimoyama Y, Nagafuchi A, Tsukita S, Hirohashi S (1993). "Cloning of the human alpha-catenin cDNA and its aberrant mRNA in a human cancer cell line". Biochem. Biophys. Res. Commun. 193 (3): 897–904. doi:10.1006/bbrc.1993.1710. PMID 8323564.
- Furukawa Y, Nakatsuru S, Nagafuchi A, Tsukita S, Muto T, Nakamura Y, Horii A (1993). "Structure, expression and chromosome assignment of the human catenin (cadherin-associated protein) alpha 1 gene (CTNNA1)". Cytogenet. Cell Genet. 65 (1–2): 74–8. doi:10.1159/000133603. PMID 8404069.
- Obama H, Ozawa M (1997). "Identification of the domain of alpha-catenin involved in its association with beta-catenin and plakoglobin (gamma-catenin)". J. Biol. Chem. 272 (17): 11017–20. doi:10.1074/jbc.272.17.11017. PMID 9110993.
- Linkels M, Bussemakers MJ, Nollet F, Ewing CM, van Roy F, Schalken JA (1997). "Molecular cloning of an alternative human alphaE-catenin cDNA". Biochem. Biophys. Res. Commun. 237 (1): 177–81. doi:10.1006/bbrc.1997.7058. PMID 9266853.
- Lewalle JM, Bajou K, Desreux J, Mareel M, Dejana E, Noël A, Foidart JM (1998). "Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro". Exp. Cell Res. 237 (2): 347–56. doi:10.1006/excr.1997.3799. hdl:2268/61990. PMID 9434630.
- Reuver SM, Garner CC (1998). "E-cadherin mediated cell adhesion recruits SAP97 into the cortical cytoskeleton". J. Cell Sci. 111 (8): 1071–80. doi:10.1242/jcs.111.8.1071. PMID 9512503.
- Watabe-Uchida M, Uchida N, Imamura Y, Nagafuchi A, Fujimoto K, Uemura T, Vermeulen S, van Roy F, Adamson ED, Takeichi M (1998). "alpha-Catenin-vinculin interaction functions to organize the apical junctional complex in epithelial cells". J. Cell Biol. 142 (3): 847–57. doi:10.1083/jcb.142.3.847. PMC 2148175. PMID 9700171.
- Roe S, Koslov ER, Rimm DL (1998). "A mutation in alpha-catenin disrupts adhesion in clone A cells without perturbing its actin and beta-catenin binding activity". Cell Adhes. Commun. 5 (4): 283–96. doi:10.3109/15419069809040298. PMID 9762469.
- Itoh M, Morita K, Tsukita S (1999). "Characterization of ZO-2 as a MAGUK family member associated with tight as well as adherens junctions with a binding affinity to occludin and alpha catenin". J. Biol. Chem. 274 (9): 5981–6. doi:10.1074/jbc.274.9.5981. PMID 10026224.