Nesprin 1α2 is essential for mouse postnatal viability and nuclear positioning in skeletal muscle

• DOI: 10.1083/jcb.201612128
• Publication Date: 2017-05-22T14:10:26Z
• Authors: Matthew J. Stroud; Wei Feng; Jianlin Zhang; Jennifer Veevers; Xi Fang; Larry Gerace; Ju Chen
• Keywords: 0301 basic medicine; 570; Biomedical and clinical sciences; Genotype; 1.1 Normal biological development and functioning; Knockout; Medical Physiology; Muscle Fibers, Skeletal; 610; Kinesins; Nerve Tissue Proteins; Inbred C57BL; Muscle Fibers; Medical and Health Sciences; Mice; 03 medical and health sciences; Myofibrils; Journal Article; Animals; Protein Interaction Domains and Motifs; Research Articles; Cell Nucleus; Mice, Knockout; Binding Sites; Biomedical and Clinical Sciences; Nuclear Proteins; Skeletal; Biological Sciences; Actins; Mice, Inbred C57BL; Biological sciences; Cytoskeletal Proteins; Phenotype; Musculoskeletal; Mutation; Biochemistry and Cell Biology; Generic health relevance; Developmental Biology; Protein Binding; Signal Transduction

The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin. However, previous studies have yet to identify which isoform is responsible. To elucidate this, we generated a series of nesprin 1 mutant mice. We showed that the actin-binding domains of nesprin 1 were dispensable, whereas nesprin 1α2, which lacks actin-binding domains, was crucial for postnatal viability, nuclear positioning, and skeletal muscle function. Furthermore, we revealed that kinesin 1 was displaced in fibers of nesprin 1α2–knockout mice, suggesting that this interaction may play an important role in positioning of myonuclei and functional skeletal muscle.