ELYS regulates the localization of LBR by modulating its phosphorylation state.
ELYS regulates the localization of LBR by modulating its phosphorylation state.
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DOI：
10.1242/jcs.190678
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发表时间：
2016-11-15
影响因子：
4
通讯作者：
Imamoto N
中科院分区：
文献类型：
--
作者：
Mimura Y;Takagi M;Clever M;Imamoto N
核纤层蛋白B受体（LBR）是一种内核膜（INM）蛋白，通过将异染色质束缚在核被膜上来促进细胞核的功能完整性。我们以前曾报道过，胚胎大分子衍生自卵黄囊（ELYS;也称为AHCTF 1），核孔复合物的组成部分，从细胞中的消耗扰乱LBR的本地化的INM，但鲜为人知的基本分子机制。在这项研究中，我们发现，ELYS的耗竭促进LBR磷酸化的残基已知被磷酸化的细胞周期蛋白依赖性激酶（CDK）和丝氨酸/精氨酸蛋白激酶1和2（SRPK 1和SRPK 2，分别）。这些磷酸化事件最有可能被蛋白磷酸酶1（PP 1）抵消，并且PP 1从细胞中的消耗一贯导致LBR的错误定位。这些观察结果指出了一种新的机制，调节LBR的本地化，这是由一个ELYS介导的磷酸化网络。INM蛋白和核孔复合物之间的这种磷酸化依赖性协调可能对细胞核的完整性很重要。 LBR的核膜定位是通过一个由ELYS调控的磷酸化网络来调节的，该磷酸化网络的缺陷会导致LBR的异常磷酸化和错误定位。
Lamin B receptor (LBR), an inner nuclear membrane (INM) protein, contributes to the functional integrity of the nucleus by tethering heterochromatin to the nuclear envelope. We have previously reported that the depletion of embryonic large molecule derived from yolk sac (ELYS; also known as AHCTF1), a component of the nuclear pore complex, from cells perturbs the localization of LBR to the INM, but little is known about the underlying molecular mechanism. In this study, we found that the depletion of ELYS promoted LBR phosphorylation at the residues known to be phosphorylated by cyclin-dependent kinase (CDK) and serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2, respectively). These phosphorylation events were most likely to be counter-balanced by protein phosphatase 1 (PP1), and the depletion of PP1 from cells consistently caused the mislocalization of LBR. These observations point to a new mechanism regulating the localization of LBR, which is governed by an ELYS-mediated phosphorylation network. This phosphorylation-dependent coordination between INM proteins and the nuclear pore complex might be important for the integrity of the nucleus. The nuclear envelope localization of LBR is regulated through a phosphorylation network governed by ELYS, and defects in this phosphorylation network induce the aberrant phosphorylation and mislocalization of LBR.
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影响因子：
3.7
作者：
Ito, Hiromi;Koyama, Yuhei;Horigome, Tsuneyoshi
通讯作者：
Horigome, Tsuneyoshi
影响因子：
4
作者：
Ma, Yan;Cai, Shang;Zhang, Chuanmao
通讯作者：
Zhang, Chuanmao
DOI：
10.4161/nucl.19595
发表时间：
2012-03-01
期刊：
Nucleus (Austin, Tex.)
影响因子：
--
作者：
Clever M;Funakoshi T;Mimura Y;Takagi M;Imamoto N
通讯作者：
Imamoto N
影响因子：
--
作者：
Moorhead, Greg B. G.;Trinkle-Mulcahy, Laura;Lamond, Angus I.
通讯作者：
Lamond, Angus I.
影响因子：
7
作者：
Kinoshita-Kikuta, Emiko;Aoki, Yuri;Koike, Tohru
通讯作者：
Koike, Tohru