Lamin B receptor plays a role in stimulating nuclear envelope production and targeting membrane vesicles to chromatin during nuclear envelope assembly through direct interaction with importin β
Lamin B receptor plays a role in stimulating nuclear envelope production and targeting membrane vesicles to chromatin during nuclear envelope assembly through direct interaction with importin β
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DOI：
10.1242/jcs.03355
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发表时间：
2007-02-01
影响因子：
4
通讯作者：
Zhang, Chuanmao
中科院分区：
文献类型：
--
作者：
Ma, Yan;Cai, Shang;Zhang, Chuanmao
核膜层蛋白B受体（Lamin B receptor， LBR）是核膜上的一种染色质和层蛋白结合蛋白，在核膜（nuclear envelope， NE）组装中起着至关重要的作用。但LBR在NE组装中的具体作用尚不清楚。在本研究中，我们发现LBR的过表达会导致膜过度生成，诱导NE内陷和膜堆积形成，而这些过程需要LBR的跨膜结构域。生化分析表明，LBR的n端结构域直接与输入蛋白β相互作用，且对输入蛋白α敏感，不依赖于输入蛋白α。通过体外NE组装试验，我们还证明，通过添加LBR n端结构域，阻断输入蛋白β上的全长LBR结合位点，可以抑制含有LBR的囊泡向输入蛋白β或ran包被的微球募集，从而形成NE结构。我们的研究结果表明，LBR通过与输入蛋白β的直接相互作用被招募到染色质上，从而促进膜囊泡的融合和NE的形成。
Lamin B receptor (LBR), a chromatin and lamin binding protein in the inner nuclear membrane, has been proposed to play a vital role in nuclear envelope (NE) assembly. But the specific role for LBR in NE assembly remains unknown. In the present study, we show that overexpression of LBR causes membrane overproduction, inducing NE invagination and membrane stack formation, and that these processes require the transmembrane domain of LBR. Biochemical analysis shows that the N-terminal domain of LBR directly interacts with importin beta in a Ran sensitive and importin alpha independent manner. Using an in vitro NE assembly assay, we also demonstrate that blocking full length LBR binding sites on importin beta, by the addition of the LBR N-terminal domain inhibits the recruitment of LBR-containing vesicles to importin beta- or Ran-coated beads to form NE structure. Our results suggest that LBR is recruited to chromatin through direct interaction with importin beta to contribute to the fusion of membrane vesicles and formation of the NE.