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      Novel plant SUN–KASH bridges are involved in RanGAP anchoring and nuclear shape determination

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          Abstract

          SUN–KASH nuclear envelope bridges formed by WIP and SUN proteins are present in the plant branch of the tree of life but have functionally diverged from their opisthokont counterparts and are involved in nuclear morphology and RanGAP–nuclear envelope association.

          Abstract

          Inner nuclear membrane Sad1/UNC-84 (SUN) proteins interact with outer nuclear membrane (ONM) Klarsicht/ANC-1/Syne homology (KASH) proteins, forming linkers of nucleoskeleton to cytoskeleton conserved from yeast to human and involved in positioning of nuclei and chromosomes. Defects in SUN–KASH bridges are linked to muscular dystrophy, progeria, and cancer. SUN proteins were recently identified in plants, but their ONM KASH partners are unknown. Arabidopsis WPP domain–interacting proteins (AtWIPs) are plant-specific ONM proteins that redundantly anchor Arabidopsis RanGTPase–activating protein 1 (AtRanGAP1) to the nuclear envelope (NE). In this paper, we report that AtWIPs are plant-specific KASH proteins interacting with Arabidopsis SUN proteins (AtSUNs). The interaction is required for both AtWIP1 and AtRanGAP1 NE localization. AtWIPs and AtSUNs are necessary for maintaining the elongated nuclear shape of Arabidopsis epidermal cells. Together, our data identify the first KASH members in the plant kingdom and provide a novel function of SUN–KASH complexes, suggesting that a functionally diverged SUN–KASH bridge is conserved beyond the opisthokonts.

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          Most cited references35

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          A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2.

          We have found that the mammalian Ran GTPase-activating protein RanGAP1 is highly concentrated at the cytoplasmic periphery of the nuclear pore complex (NPC), where it associates with the 358-kDa Ran-GTP-binding protein RanBP2. This interaction requires the ATP-dependent posttranslational conjugation of RanGAP1 with SUMO-1 (for small ubiquitin-related modifier), a novel protein of 101 amino acids that contains low but significant homology to ubiquitin. SUMO-1 appears to represent the prototype for a novel family of ubiquitin-related protein modifiers. Inhibition of nuclear protein import resulting from antibodies directed at NPC-associated RanGAP1 cannot be overcome by soluble cytosolic RanGAP1, indicating that GTP hydrolysis by Ran at RanBP2 is required for nuclear protein import.
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            Sizing up the nucleus: nuclear shape, size and nuclear-envelope assembly.

            The nucleus is one of the most prominent cellular organelles, yet surprisingly little is known about how it is formed, what determines its shape and what defines its size. As the nuclear envelope (NE) disassembles in each and every cell cycle in metazoans, the process of rebuilding the nucleus is crucial for proper development and cell proliferation. In this Commentary, we summarize what is known about the regulation of nuclear shape and size, and highlight recent findings that shed light on the process of building a nucleus, including new discoveries related to NE assembly and the relationship between the NE and the endoplasmic reticulum (ER). Throughout our discussion, we note interesting aspects of nuclear structure that have yet to be resolved. Finally, we present an idea - which we refer to as ;the limited flat membrane hypothesis' - to explain the formation of a single nucleus that encompasses of all of the cell's chromosomes following mitosis.
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              Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.

              Mutations in the lamin A/C gene (LMNA) cause a variety of human diseases including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome. The tissue-specific effects of lamin mutations are unclear, in part because the function of lamin A/C is incompletely defined, but the many muscle-specific phenotypes suggest that defective lamin A/C could increase cellular mechanical sensitivity. To investigate the role of lamin A/C in mechanotransduction, we subjected lamin A/C-deficient mouse embryo fibroblasts to mechanical strain and measured nuclear mechanical properties and strain-induced signaling. We found that Lmna-/- cells have increased nuclear deformation, defective mechanotransduction, and impaired viability under mechanical strain. NF-kappaB-regulated transcription in response to mechanical or cytokine stimulation was attenuated in Lmna-/- cells despite increased transcription factor binding. Lamin A/C deficiency is thus associated with both defective nuclear mechanics and impaired mechanically activated gene transcription. These findings suggest that the tissue-specific effects of lamin A/C mutations observed in the laminopathies may arise from varying degrees of impaired nuclear mechanics and transcriptional activation.
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                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                23 January 2012
                : 196
                : 2
                : 203-211
                Affiliations
                [1 ]Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210
                [2 ]Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Headington Campus, Oxford OX3 OBP, England, UK
                Author notes
                Correspondence to Iris Meier: meier.56@ 123456osu.edu
                Article
                201108098
                10.1083/jcb.201108098
                3265956
                22270916
                374d351b-df39-4d40-8eeb-372e93776194
                © 2012 Zhou et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                : 15 August 2011
                : 20 December 2011
                Categories
                Research Articles
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                Cell biology
                Cell biology

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