Abstract
Nesprins form a novel class of nuclear envelope-anchored spectrin-repeat proteins. We show that a direct association of their highly conserved C-terminal luminal domain with the inner nuclear membrane protein Sun1 mediates their nuclear envelope localisation. In Nesprin-1 and Nesprin-2 the conserved C-terminal amino acids PPPX are essential for the interaction with a C-terminal region in Sun1. In fact, Sun1 is required for the proper nuclear envelope localisation of Nesprin-2 as shown using dominant-negative mutants and by knockdown of Sun1 expression. Sun1 itself does not require functional A-type lamins for its localisation at the inner nuclear membrane in mammalian cells. Our findings propose a conserved nuclear anchorage mechanism between Caenorhabditis elegans and mammals and suggest a model in which Sun1 serves as a ;structural bridge' connecting the nuclear interior with the actin cytoskeleton.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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COS Cells
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism
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Cell Nucleus / metabolism
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Chlorocebus aethiops
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Cloning, Molecular
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Cytoskeletal Proteins
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HeLa Cells
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Humans
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Intracellular Membranes / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C3H
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Mice, Knockout
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Models, Biological
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nuclear Envelope / classification
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Nuclear Envelope / metabolism*
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Nuclear Envelope / ultrastructure
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
Substances
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Cytoskeletal Proteins
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Membrane Proteins
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Microfilament Proteins
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Recombinant Fusion Proteins
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SUN1 protein, human
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SUN1 protein, mouse
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SYNE1 protein, human
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SYNE2 protein, human
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Syne1 protein, mouse
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Syne2 protein, mouse