SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton

被引:391
作者
Haque, Farhana
Lloyd, David J.
Smallwood, Dawn T.
Dent, Carolyn L.
Shanahan, Catherine M.
Fry, Andrew M.
Trembath, Richard C.
Shackleton, Sue
机构
[1] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England
[2] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England
[3] Univ Cambridge, Div Cardiovasc Med, Dept Med, Cambridge CB2 2QQ, England
基金
英国惠康基金;
关键词
D O I
10.1128/MCB.26.10.3738-3751.2006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear migration and positioning within cells are critical for many developmental processes and are governed by the cytoskeletal network. Although mechanisms of nuclear-cytoskeletal attachment are unclear, growing evidence links a novel family of nuclear envelope (NE) proteins that share a conserved C-terminal SUN (Sad1/UNC-84 homology) domain. Analysis of Caenorhabditis elegans mutants has implicated UNC-84 in actin-mediated nuclear positioning by regulating NE anchoring of a giant actin-binding protein, ANC-1. Here, we report the identification of SUN1 as a lamin A-binding protein in a yeast two-hybrid screen. We demonstrate that SUN1 is an integral membrane protein located at the inner nuclear membrane. While the N-terminal domain of SUN1 is responsible for detergent-resistant association with the nuclear lamina and lamin A binding, lamin A/C expression is not required for SUN1 NE localization. Furthermore, SUN1 does not interact with type B lamins, suggesting that NE localization is ensured by binding to an additional nuclear component(s), most likely chromatin. Importantly, we find that the luminal C-terminal domain of SUN1 interacts with the mammalian ANC-1 homologs nesprins 1 and 2 via their conserved KASH domain. Our data provide evidence of a physical nuclear-cytoskeletal connection that is likely to be a key mechanism in nuclear-cytoplasmic communication and regulation of nuclear position.
引用
收藏
页码:3738 / 3751
页数:14
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