Nesprin‐1α self‐associates and binds directly to emerin and lamin A in vitro

FEBS Letters

Holaska, James M²  Wilson, Katherine L²  Mislow, John M.K³  Lee, Kenneth K²  McNally, Elizabeth M¹  Segura-Totten, Miriam²  Kim, Marian S¹ 

[1] Department of Medicine, Section of Cardiology, The University of Chicago, 5841 S. Maryland, MC 6088, Rm G611, Chicago, IL 60637, USA;Department of Cell Biology, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA;Department of Pathology, The University of Chicago, Chicago, IL 60637, USA

关键词: Spectrin repeat;    Crosslinker;    Inner nuclear membrane;    Lamin A/C;    Emerin;    Nuclear envelope;    Emery–Dreifuss muscular dystrophy;    SR;    spectrin repeat;    INM;    inner nuclear membrane;    BAF;    barrier-to-autointegration factor;   

DOI  :  10.1016/S0014-5793(02)03105-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Nesprin-1α is a spectrin repeat (SR)-containing, transmembrane protein of the inner nuclear membrane, and is highly expressed in muscle cells. A yeast two-hybrid screen for nesprin-1α-interacting proteins showed that nesprin-1α interacted with itself. Blot overlay experiments revealed that nesprin-1α's third SR binds the fifth SR. The carboxy-terminal half of nesprin-1α directly bound lamin A, a nuclear intermediate filament protein. Biochemical analysis demonstrated that nesprin-1α dimers bind directly to the nucleoplasmic domain of emerin, an inner nuclear membrane protein, with an affinity of 4 nM. Binding was optimal for full nucleoplasmic dimers of nesprin-1α, since nesprin fragments SR1-5 and SR5-7 bound emerin as monomers with affinities of 53 nM and 250 mM, respectively. We propose that membrane-anchored nesprin-1α antiparallel dimers interact with both emerin and lamin A to provide scaffolding at the inner nuclear membrane.

【 授权许可】

Unknown