The Amotl2 Gene Inhibits Wnt/β-catenin Signaling and Regulates Embryonic Development in Zebrafish

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Feb 25

PMID 22362771

Citations 27

Authors

Zhiqiang Li

Yeqi Wang

Min Zhang

Pengfei Xu

Huizhe Huang

Di Wu

Anming Meng

Affiliations

Soon will be listed here.

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.

Citing Articles

Biliary atresia: insights into mechanisms using a toxic model of the disease including Wnt and Hippo signaling pathways and microtubules.

Fried S, Har-Zahav A, Hamudi Y, Mahameed S, Mansur R, Dotan M Pediatr Res. 2024; 97(1):184-194.

PMID: 38914763 PMC: 11798875. DOI: 10.1038/s41390-024-03335-9.

Regulation of YAP and Wnt signaling by the endosomal protein MAMDC4.

Cox C, Wu M, Padilla-Rodriguez M, Blum I, Momtaz S, Mitchell S PLoS One. 2024; 19(5):e0296003.

PMID: 38787854 PMC: 11125477. DOI: 10.1371/journal.pone.0296003.

Role of angiomotin family members in human diseases (Review).

Wang H, Ye M, Jin X Exp Ther Med. 2024; 27(6):258.

PMID: 38766307 PMC: 11099588. DOI: 10.3892/etm.2024.12546.

Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2.

Bulos M, Grzelak E, Li-Ma C, Chen E, Hull M, Johnson K Elife. 2023; 12.

PMID: 38126343 PMC: 10735217. DOI: 10.7554/eLife.88508.

CircAMOTL1 RNA and AMOTL1 Protein: Complex Functions of Gene Products.

Sadlak J, Joshi I, Proszynski T, Kischel A Int J Mol Sci. 2023; 24(3).

PMID: 36768425 PMC: 9916871. DOI: 10.3390/ijms24032103.

References

Aase K, Ernkvist M, Ebarasi L, Jakobsson L, Majumdar A, Yi C . Angiomotin regulates endothelial cell migration during embryonic angiogenesis. Genes Dev. 2007; 21(16):2055-68. PMC: 1948860. DOI: 10.1101/gad.432007. View

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

Lekven A, Thorpe C, Waxman J, Moon R . Zebrafish wnt8 encodes two wnt8 proteins on a bicistronic transcript and is required for mesoderm and neurectoderm patterning. Dev Cell. 2001; 1(1):103-14. DOI: 10.1016/s1534-5807(01)00007-7. View

Zheng Y, Vertuani S, Nystrom S, Audebert S, Meijer I, Tegnebratt T . Angiomotin-like protein 1 controls endothelial polarity and junction stability during sprouting angiogenesis. Circ Res. 2009; 105(3):260-70. DOI: 10.1161/CIRCRESAHA.109.195156. View

Ding Q, Xia W, Liu J, Yang J, Lee D, Xia J . Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin. Mol Cell. 2005; 19(2):159-70. DOI: 10.1016/j.molcel.2005.06.009. View

Bellipanni G, Varga M, Maegawa S, Imai Y, Kelly C, Myers A . Essential and opposing roles of zebrafish beta-catenins in the formation of dorsal axial structures and neurectoderm. Development. 2006; 133(7):1299-309. DOI: 10.1242/dev.02295. View

Leung T, Soll I, Arnold S, Kemler R, Driever W . Direct binding of Lef1 to sites in the boz promoter may mediate pre-midblastula-transition activation of boz expression. Dev Dyn. 2003; 228(3):424-32. DOI: 10.1002/dvdy.10408. View

Heller B, Adu-Gyamfi E, Smith-Kinnaman W, Babbey C, Vora M, Xue Y . Amot recognizes a juxtanuclear endocytic recycling compartment via a novel lipid binding domain. J Biol Chem. 2010; 285(16):12308-20. PMC: 2852970. DOI: 10.1074/jbc.M109.096230. View

Yi C, Troutman S, Fera D, Stemmer-Rachamimov A, Avila J, Christian N . A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell. 2011; 19(4):527-40. PMC: 3075552. DOI: 10.1016/j.ccr.2011.02.017. View

10.

Zhao B, Li L, Lu Q, Wang L, Liu C, Lei Q . Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev. 2011; 25(1):51-63. PMC: 3012936. DOI: 10.1101/gad.2000111. View

11.

Xiong B, Rui Y, Zhang M, Shi K, Jia S, Tian T . Tob1 controls dorsal development of zebrafish embryos by antagonizing maternal beta-catenin transcriptional activity. Dev Cell. 2006; 11(2):225-38. DOI: 10.1016/j.devcel.2006.06.012. View

12.

Chan S, Lim C, Chong Y, Pobbati A, Huang C, Hong W . Hippo pathway-independent restriction of TAZ and YAP by angiomotin. J Biol Chem. 2011; 286(9):7018-26. PMC: 3044958. DOI: 10.1074/jbc.C110.212621. View

13.

Ernkvist M, Birot O, Sinha I, Veitonmaki N, Nystrom S, Aase K . Differential roles of p80- and p130-angiomotin in the switch between migration and stabilization of endothelial cells. Biochim Biophys Acta. 2008; 1783(3):429-37. DOI: 10.1016/j.bbamcr.2007.11.018. View

14.

Zhang L, Zhou H, Su Y, Sun Z, Zhang H, Zhang L . Zebrafish Dpr2 inhibits mesoderm induction by promoting degradation of nodal receptors. Science. 2004; 306(5693):114-7. DOI: 10.1126/science.1100569. View

15.

Imajo M, Miyatake K, Iimura A, Miyamoto A, Nishida E . A molecular mechanism that links Hippo signalling to the inhibition of Wnt/β-catenin signalling. EMBO J. 2012; 31(5):1109-22. PMC: 3297994. DOI: 10.1038/emboj.2011.487. View

16.

Heisenberg C, Brand M, Jiang Y, Warga R, Beuchle D, van Eeden F . Genes involved in forebrain development in the zebrafish, Danio rerio. Development. 1996; 123:191-203. DOI: 10.1242/dev.123.1.191. View

17.

Rottbauer W, Saurin A, Lickert H, Shen X, Burns C, Wo Z . Reptin and pontin antagonistically regulate heart growth in zebrafish embryos. Cell. 2002; 111(5):661-72. DOI: 10.1016/s0092-8674(02)01112-1. View

18.

Baum B, Georgiou M . Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling. J Cell Biol. 2011; 192(6):907-17. PMC: 3063136. DOI: 10.1083/jcb.201009141. View

19.

MacDonald B, Tamai K, He X . Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009; 17(1):9-26. PMC: 2861485. DOI: 10.1016/j.devcel.2009.06.016. View

20.

Heisenberg C, Houart C, Take-Uchi M, Rauch G, Young N, Coutinho P . A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes Dev. 2001; 15(11):1427-34. PMC: 312705. DOI: 10.1101/gad.194301. View