Nucleocytoplasmic connections and deafness
Howard J. Worman, Neil Segil
Howard J. Worman, Neil Segil
Published January 25, 2013
Citation Information: J Clin Invest. 2013;123(2):553-555. https://doi.org/10.1172/JCI67454.
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Commentary

Nucleocytoplasmic connections and deafness

Abstract

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.

Authors

Howard J. Worman, Neil Segil

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Figure 1

The LINC complex and its connection to the nuclear lamina and cytoskeletal components.

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The LINC complex and its connection to the nuclear lamina and cytoskelet...
The carboxyl termini of Suns, integral proteins of the inner nuclear membrane, bind within the perinuclear space to the carboxyl terminal KASH domain of nesprins, which are transmembrane proteins localized to the outer nuclear membrane. The amino termini of Suns bind to the nuclear lamina, an intermediate filament meshwork of lamins on the inner aspect of the inner nuclear membrane. Different nesprins have variable cytoplasmic amino terminal domains that interact with different cytoskeletal elements. Nesprin-4, shown in this diagram, binds to kinesin, which in turn can associate with microtubules.