title: Nesprin provides elastic properties to muscle nuclei by cooperating with spectraplakin and EB1.
abstract: Muscle nuclei are exposed to variable cytoplasmic strain produced by muscle contraction and relaxation, but their morphology remains stable. Still, the mechanism responsible for maintaining myonuclear architecture, and its importance, is currently elusive. Herein, we uncovered a unique myonuclear scaffold in Drosophila melanogaster larval muscles, exhibiting both elastic features contributed by the stretching capacity of MSP300 (nesprin) and rigidity provided by a perinuclear network of microtubules stabilized by Shot (spectraplakin) and EB1. Together, they form a flexible perinuclear shield that protects myonuclei from intrinsic or extrinsic forces. The loss of this scaffold resulted in significantly aberrant nuclear morphology and subsequently reduced levels of essential nuclear factors such as lamin A/C, lamin B, and HP1. Overall, we propose a novel mechanism for maintaining myonuclear morphology and reveal its critical link to correct levels of nuclear factors in differentiated muscle fibers. These findings may shed light on the underlying mechanism of various muscular dystrophies.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Shuoshuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Adriana
authors.initials: A
authors.lastname: Reuveny
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel Talila.Volk@weizmann.ac.il.
authors.forename: Talila
authors.initials: T
authors.lastname: Volk
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism* / Q000648:ultrastructure; D004548:Elasticity; D034882:Lamins / Q000378:metabolism; D007814:Larva / Q000378:metabolism / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000378:metabolism* / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000648:ultrastructure; D009124:Muscle Proteins / Q000502:physiology*; D054792:Muscle, Striated / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport
chemical_list: D000199:Actins; D029721:Drosophila Proteins; C000593037:EB1 protein, Drosophila; D034882:Lamins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C079806:Msp300 protein, Drosophila; D009124:Muscle Proteins; C450828:shot protein, Drosophila