LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins
LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins
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DOI：
10.1242/jcs.02701
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发表时间：
2005-12-15
影响因子：
4
通讯作者：
Gotzmann, J
中科院分区：
文献类型：
--
作者：
Brachner, A;Reipert, S;Gotzmann, J
LEM（lamina-associated polypeptide-emerin-MAN 1）结构域是核内膜和核质中一组核纤层蛋白相互作用蛋白共有的基序。LEM结构域介导与DNA交联蛋白，自整合屏障因子（BAF）的结合。我们描述了一种新的，普遍表达的LEM结构域蛋白，LEM 2，这是结构相关的MAN 1。LEM 2含有一个N-末端LEM基序，两个预测的跨膜结构域和一个与MAN 1高度同源的MAN 1-Src 1 p C-末端（MSC）结构域，但缺乏MAN 1特异性的C-末端RNA识别基序。毛地黄皂苷处理的细胞和亚细胞分级的免疫荧光显微镜鉴定LEM 2作为层相关蛋白驻留在INM。LEM 2在体外与核纤层蛋白C尾结合。LEM 2靶向核被膜需要A型核纤层蛋白，并由N末端和跨膜结构域介导。高度过表达的LEM 2在核膜处聚集成斑块，并在相邻细胞的核之间形成膜桥。LEM 2结构募集A型核纤层蛋白、emerin、MAN 1和BAF，而排除核纤层蛋白B和核纤层蛋白B受体。我们的数据确定LEM 2作为一种新的A型层粘连蛋白相关的INM蛋白参与核结构组织。
The LEM (lamina-associated polypeptide-emerin-MAN1) domain is a motif shared by a group of lamin-interacting proteins in the inner nuclear membrane (INM) and in the nucleoplasm. The LEM domain mediates binding to a DNA-crosslinking protein, barrier-to-autointegration factor (BAF). We describe a novel, ubiquitously expressed LEM domain protein, LEM2, which is structurally related to MAN1. LEM2 contains an N-terminal LEM motif, two predicted transmembrane domains and a MAN1-Src1p C-terminal (MSC) domain highly homologous to MAN1, but lacks the MAN1-specific C-terminal RNA-recognition motif. Immunofluoreseence microscopy of digitonin-treated cells and subcellular fractionation identified LEM2 as a lamina-associated protein residing in the INM. LEM2 binds to the lamin C tail in vitro. Targeting of LEM2 to the nuclear envelope requires A-type lamins and is mediated by the N-terminal and transmembrane domains. Highly overexpressed LEM2 accumulates in patches at the nuclear envelope and forms membrane bridges between nuclei of adjacent cells. LEM2 structures recruit A-type lamins, emerin, MAN1 and BAF, whereas lamin B and lamin B receptor are excluded. Our data identify LEM2 as a novel A-type-lamin-associated INM protein involved in nuclear structure organization.