title: Syne-1 and Syne-2 play crucial roles in myonuclear anchorage and motor neuron innervation.
abstract: Proper nuclear positioning is important to cell function in many biological processes during animal development. In certain cells, the KASH-domain-containing proteins have been shown to be associated with the nuclear envelope, and to be involved in both nuclear anchorage and migration. We investigated the mechanism and function of nuclear anchorage in skeletal muscle cells by generating mice with single and double-disruption of the KASH-domain-containing genes Syne1 (also known as Syne-1) and Syne2 (also known as Syne-2). We showed that the deletion of the KASH domain of Syne-1 abolished the formation of clusters of synaptic nuclei and disrupted the organization of non-synaptic nuclei in skeletal muscle. Further analysis indicated that the loss of synaptic nuclei in Syne-1 KASH-knockout mice significantly affected the innervation sites and caused longer motor nerve branches. Although disruption of neither Syne-1 nor Syne-2 affected viability or fertility, Syne-1; Syne-2 double-knockout mice died of respiratory failure within 20 minutes of birth. These results suggest that the KASH-domain-containing proteins Syne-1 and Syne-2 play crucial roles in anchoring both synaptic and non-synaptic myonuclei that are important for proper motor neuron innervation and respiration.
authors.affiliation: Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai, 200433, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Zhang
authors.forename: Rener
authors.initials: R
authors.lastname: Xu
authors.forename: Binggen
authors.initials: B
authors.lastname: Zhu
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Ding
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
authors.forename: Tian
authors.initials: T
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002467:Cell Nucleus / Q000502:physiology*; D003598:Cytoskeletal Proteins; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C485901:Syne1 protein, mouse; C485903:Syne2 protein, mouse