title: SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice.
abstract: How the nuclei in mammalian skeletal muscle fibers properly position themselves relative to the cell body is an interesting and important cell biology question. In the syncytial skeletal muscle cells, more than 100 nuclei are evenly distributed at the periphery of each cell, with 3-8 nuclei anchored beneath the neuromuscular junction (NMJ). Our previous studies revealed that the KASH domain-containing Syne-1/Nesprin-1 protein plays an essential role in anchoring both synaptic and nonsynaptic myonuclei in mice. SUN domain-containing proteins (SUN proteins) have been shown to interact with KASH domain-containing proteins (KASH proteins) at the nuclear envelope (NE), but their roles in nuclear positioning in mice are unknown. Here we show that the synaptic nuclear anchorage is partially perturbed in Sun1, but not in Sun2, knockout mice. Disruption of 3 or all 4 Sun1/2 wild-type alleles revealed a gene dosage effect on synaptic nuclear anchorage. The organization of nonsynaptic nuclei is disrupted in Sun1/2 double-knockout (DKO) mice as well. We further show that the localization of Syne-1 to the NE of muscle cells is disrupted in Sun1/2 DKO mice. These results clearly indicate that SUN1 and SUN2 function critically in skeletal muscle cells for Syne-1 localization at the NE, which is essential for proper myonuclear positioning.
authors.affiliation: Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Lei
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Ding
authors.forename: Xue
authors.initials: X
authors.lastname: Guo
authors.forename: Muyun
authors.initials: M
authors.lastname: Chen
authors.forename: Binggen
authors.initials: B
authors.lastname: Zhu
authors.forename: Tian
authors.initials: T
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Rener
authors.initials: R
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C464932:SUN1 protein, mouse; C520338:Sun2 protein, mouse; C485901:Syne1 protein, mouse; D034501:Telomere-Binding Proteins