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

Mol Cell Biol. 2006 May;26(10):3738-51. doi: 10.1128/MCB.26.10.3738-3751.2006.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism*
  • Cytoskeletal Proteins
  • Cytoskeleton / metabolism*
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Lamin Type A / metabolism*
  • Mice
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques


  • Cytoskeletal Proteins
  • Lamin Type A
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • SUN1 protein, mouse
  • Syne1 protein, mouse
  • Syne2 protein, mouse