Department of Medicine, College of Physician and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
J Clin Invest. 2013 Feb;123(2):553-5. doi: 10.1172/JCI67454. Epub 2013 Jan 25.
The linker of nucleoskeleton and cytoskeleton (LINC) complex connects the nuclear lamina to the cytoskeleton, in part to aid in nuclear positioning. Mutations in genes encoding LINC complex and lamina components cause a range of human diseases. In this issue of the JCI, Horn et al. report that mutations in the gene SYNE4 encoding the LINC complex protein nesprin-4 lead to progressive high-frequency hearing loss. Further, in mice deficient in nesprin-4 and Sun1, another LINC complex component, outer hair cells of the cochlea form normally during development, but die in the early postnatal weeks. These results link improper nuclear positioning specifically to the death of outer hair cells in the organ of Corti and ultimately to deafness.
核骨架-细胞骨架连接复合物（LINC）将核层与细胞骨架连接起来，部分有助于核定位。编码 LINC 复合物和层粘连蛋白成分的基因突变会导致一系列人类疾病。在本期 JCI 中，Horn 等人报告说，编码 LINC 复合物蛋白 nesprin-4 的基因 SYNE4 的突变导致进行性高频听力损失。此外，在 nesprin-4 和另一个 LINC 复合物成分 Sun1 缺失的小鼠中，耳蜗的外毛细胞在发育过程中正常形成，但在出生后的早期几周内死亡。这些结果将核定位不当与 Corti 器官中外毛细胞的死亡以及最终的耳聋联系起来。
