Amotl2 gene inhibits Wnt/beta-catenin signaling and regulates embryonic development in zebrafish embryoys
- Authors
- Li, Z., Wang, Y., Zhang, M., Xu, P., Huang, H., Wu, D., and Meng, A.
- ID
- ZDB-PUB-120301-7
- Date
- 2012
- Source
- The Journal of biological chemistry 287(16): 13005-13015 (Journal)
- Registered Authors
- Huang, Huizhe, Meng, Anming, Wu, Di, Xu, Pengfei, Zhang, Min
- Keywords
- beta-canetin, embryo, endosomes, Wnt signaling, zebrafish, angiomotin-like2
- MeSH Terms
-
- Animals
- Cell Nucleus/metabolism
- Cytoplasm/metabolism
- Endosomes/metabolism
- Eye/embryology
- Gene Expression Regulation, Developmental/physiology*
- HEK293 Cells
- Humans
- Membrane Proteins/chemistry
- Membrane Proteins/genetics*
- Membrane Proteins/metabolism*
- Phenotype
- Protein Structure, Tertiary
- Up-Regulation/physiology
- Wnt Signaling Pathway/physiology*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- beta Catenin/metabolism*
- PubMed
- 22362771 Full text @ J. Biol. Chem.
The Motin family proteins can regulate cell polarity, cell mobility and proliferation during embryonic development by controlling distinct signaling pathways. In this study, we demonstrate that amotl2 knockdown in zebrafish wild-type embryos results in embryonic dorsalization and this effect can be antagonized by co-knockdown of the dorsal inducer β-catenin2. Overexpression of amotl2 in masterblind (mbl) homozygous embryos, in which canonical Wnt signaling is up-regulated due to an axin1 mutation, transforms eyeless phenotype into smaller eyes, whereas co-knockdown of amot, amotl1 and amotl2 leads to development of smaller eyes in mbl heterozygotes. In cultured mammalian cells, Motin family members all possess the ability to attenuate Wnt/β-catenin signaling. Focusing on Amotl2, we show that Amotl2 can associate with and trap β-catenin in the Rab11-positive recycling endosomes, and as a result, the amount of β-catenin in the cytosol and nucleus is reduced. Thus, our findings provide novel insights into functions of Motin family members and regulation of Wnt/β-catenin signaling.