The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope.
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.
Mesh Terms:
Animals, COS Cells, Caenorhabditis elegans, Cell Nucleus, Cercopithecus aethiops, Cloning, Molecular, Hela Cells, Humans, Intracellular Membranes, Membrane Proteins, Mice, Mice, Inbred C3H, Mice, Knockout, Microfilament Proteins, Microtubule-Associated Proteins, Models, Biological, Nerve Tissue Proteins, Nuclear Envelope, Nuclear Proteins, Recombinant Fusion Proteins
Animals, COS Cells, Caenorhabditis elegans, Cell Nucleus, Cercopithecus aethiops, Cloning, Molecular, Hela Cells, Humans, Intracellular Membranes, Membrane Proteins, Mice, Mice, Inbred C3H, Mice, Knockout, Microfilament Proteins, Microtubule-Associated Proteins, Models, Biological, Nerve Tissue Proteins, Nuclear Envelope, Nuclear Proteins, Recombinant Fusion Proteins
J. Cell. Sci.
Date: Aug. 01, 2005
PubMed ID: 16079285
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