Caveolin-1 regulates dorsoventral patterning through direct interaction with beta-catenin in zebrafish.
Caveolin-1 (Cav-1) is the principal component of plasma membrane caveolae that negatively regulates a number of cellular signaling events including canonical Wnt signaling. Activation of the Wnt/beta-catenin pathway is essential for dorsal organizer formation and specification in early vertebrate embryos, but it remains not well understood what controls dorsal activity of maternal beta-catenin and how Cav-1 functions in zebrafish embryogenesis. Here, we report that Cav-1 is required for proper dorsoventral patterning in zebrafish. Both Wnt and BMP signals act coordinately to negatively control transcriptional expression of cav-1 during embryonic development. Ectopic expression of Cav-1alpha or -1beta resulted in formation of typical ventralized embryos, whereas Cav-1 knockdown led to abnormal embryos with expanded expression of dorsal genes. Cav-1 overexpression disrupts the nuclear translocation of beta-catenin through the interaction of its scaffolding domain with Cav-1 binding motif of beta-catenin. This reciprocal interaction is necessary for the ventralizing activity of Cav-1. We have further demonstrated that human Cav-1 proteins have conserved ventralizing activity in zebrafish embryogenesis. Thus, maternally expressed zebrafish Cav-1 regulates dorsoventral patterning by limiting nuclear translocation of active beta-catenin.
Mo
Saijun
S
Key Laboratory of Biodiversity and Conservation of Aquatic Organism, Chinese Academy of Sciences, Wuhan, Hubei 430072, PR China.
Wang
Lu
L
Li
Qing
Q
Li
Jie
J
Li
Yuanyuan
Y
Thannickal
Victor J
VJ
Cui
Zongbin
Z
D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000818:Animals; D019521:Body Patterning; D051242:Caveolin 1 / Q000378:metabolism*; D015509:Developmental Biology / Q000379:methods; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D015027:Zebrafish; D051176:beta Catenin / Q000378:metabolism*
D051242:Caveolin 1; D051176:beta Catenin