Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin.
Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin.
复制标题
DOI：
10.1038/mp.2014.42
复制
发表时间：
2015-03
影响因子：
11
通讯作者：
Tsai LH
中科院分区：
文献类型：
--
作者：
Durak O;de Anda FC;Singh KK;Leussis MP;Petryshen TL;Sklar P;Tsai LH
锚蛋白-G是神经元中轴突起始段形成所需的支架蛋白。最近的全基因组关联研究和全外显子组测序已经确定ANK 3，编码ankrex-G的基因，是多种神经精神疾病如双相情感障碍（BD），精神分裂症和自闭症谱系障碍（ASD）的风险基因。在这里，我们描述了一个新的作用，在神经前体细胞增殖发育皮层中的ankrex-G。我们发现，锚蛋白-G通过改变增殖细胞中β-连环蛋白的亚细胞定位和可用性来调节经典Wnt信号传导。锚蛋白-G功能丧失增加细胞核中的β-连环蛋白水平，从而促进神经祖细胞增殖。重要的是，增殖异常可以通过减少Wnt途径信号传导来挽救。总之，这些结果表明，anke-G是适当的大脑发育所必需的。
Ankyrin-G is a scaffolding protein required for the formation of the axon initial segment in neurons. Recent genome-wide association studies and whole-exome sequencing have identified ANK3, the gene coding for ankyrin-G, to be a risk gene for multiple neuropsychiatric disorders such as bipolar disorder (BD), schizophrenia, and autism spectrum disorder (ASD). Here, we describe a novel role for ankyrin-G in neural progenitor proliferation in the developing cortex. We found that ankyrin-G regulates canonical Wnt signaling by altering the subcellular localization and availability of β-catenin in proliferating cells. Ankyrin-G loss-of-function increases β-catenin levels in the nucleus, thereby promoting neural progenitor proliferation. Importantly, abnormalities in proliferation can be rescued by reducing Wnt pathway signaling. Together, these results suggest that ankyrin-G is required for proper brain development.
登录
查看更多内容
影响因子：
16.2
作者：
Bultje, Ronald S.;Castaneda-Castellanos, David R.;Jan, Lily Yen;Jan, Yuh-Nung;Kriegstein, Arnold R.;Shi, Song-Hai
通讯作者：
Shi, Song-Hai
影响因子：
64.8
作者：
Insel, Thomas R.
通讯作者：
Insel, Thomas R.
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
影响因子：
0.9
作者：
Hatzimanolis A;Smyrnis N;Avramopoulos D;Stefanis CN;Evdokimidis I;Stefanis NC
通讯作者：
Stefanis NC
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R