title: The Amotl2 gene inhibits Wnt/β-catenin signaling and regulates embryonic development in zebrafish.
abstract: 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.
authors.affiliation: State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.forename: Yeqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.forename: Huizhe
authors.initials: H
authors.lastname: Huang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: D000091082:Angiomotins; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005123:Eye / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D015854:Up-Regulation / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000091082:Angiomotins; D008565:Membrane Proteins; D029961:Zebrafish Proteins; C519597:amotl2a protein, zebrafish; D051176:beta Catenin; C495269:ctnnb1 protein, zebrafish