Complete functional segregation of planarian beta-catenin-1 and -2 in mediating Wnt signaling and cell adhesion.
beta-Catenin is a bifunctional protein participating in both cell adhesion and canonical Wnt signaling. In cell adhesion, it bridges the transmembrane cadherin and the actin-binding protein alpha-catenin and is essential for adherens junction formation, whereas in canonical Wnt signaling, it shuttles between the cytosol and nucleus and functions as an essential transcriptional activator. Schmidtea mediterranea beta-catenin-1 was identified as a determinant of antero-posterior polarity during body regeneration by mediating Wnt signaling. Here we show that S. mediterranea beta-catenin-2 is specifically expressed in epithelial cells in the gut and pharynx, where it has a putative role in mediating cell adhesion. We show evidence that planarian beta-catenin-1 and -2 have distinct biochemical properties. beta-Catenin-1 can interact with the components of the canonical Wnt signaling pathway but not with alpha-catenin, whereas beta-catenin-2 interacts with cell adhesion molecules, including E-cadherin and alpha-catenin, but not with Wnt signaling components. Consistent with their specific function, beta-catenin-1 is a potent transcriptional activator, whereas beta-catenin-2 has no transcriptional activity. Protein sequence alignment also indicates that the planarian beta-catenin-1 and -2 retain distinct critical residues and motifs, which are in agreement with the differences in their biochemical properties. At last, phylogenetic analysis reveals a probable Platyhelminthes- specific structural and functional segregation from which the monofunctional beta-catenins evolved. Our results thus identify the first two monofunctional beta-catenins in metazoans.
Protein Science Laboratory of the Ministry of Education, Tsinghua University, Beijing 100084, China.
Guoliang
G
Chai
Changxin
C
Ma
Kai
K
Bao
Liang
L
Zheng
Xinquan
X
Wang
Zhirong
Z
Sun
Emili
E
Salò
Teresa
T
Adell
Wei
W
Wu
D020816:Amino Acid Motifs; D000818:Animals; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D010932:Planarians / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D014018:Tissue Distribution; D051153:Wnt Proteins / Q000378:metabolism*; D014981:Xenopus; D051176:beta Catenin / Q000378:metabolism*
D051153:Wnt Proteins; D051176:beta Catenin