title: Coupling of the nucleus and cytoplasm: role of the LINC complex.
abstract: The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH(2)-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A.A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118:3419-3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).
authors.affiliation: Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610.
authors.forename: Melissa
authors.initials: M
authors.lastname: Crisp
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Kyle
authors.initials: K
authors.lastname: Roux
authors.forename: J B
authors.initials: JB
authors.lastname: Rattner
authors.forename: Catherine
authors.initials: C
authors.lastname: Shanahan
authors.forename: Brian
authors.initials: B
authors.lastname: Burke
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Stahl
authors.forename: Didier
authors.initials: D
authors.lastname: Hodzic
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000502:physiology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D046911:Macromolecular Substances / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008840:Microfilament Proteins / Q000032:analysis / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D009685:Nuclear Envelope / Q000737:chemistry* / Q000502:physiology; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D016415:Sequence Alignment
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C506117:SUN1 protein, human; C413025:SUN2 protein, human; C485904:SYNE2 protein, human