Muscular dystrophy-associated lamin variants disrupt cellular organization through a nucleolar-ribosomal axis.

Authors

Xiangyi Ding, Sweta Kumari, Ellen F Gregory, Daniel A Starr, G W Gant Luxton

Published in

Science advances. Volume 12. Issue 35. Pages eaec9028. Aug 28, 2026. Epub Aug 26, 2026.

Abstract

Emery-Dreifuss muscular dystrophy (EDMD) arises from mutations in nuclear lamins or emerin. Current pathological models emphasize defective nuclear mechanics and transcriptional regulation, yet these mechanisms cannot explain how lamina defects propagate across the cell to produce the complex pathology of laminopathies. Here, we reveal an emerging pathway linking nuclear lamina dysfunction to cytoplasmic reorganization. Using Caenorhabditis elegans EDMD models, we show that disease-linked lamin variants reduce cytoplasmic mesoscale crowding, increase molecular diffusivity, and disrupt nuclear positioning and endoplasmic reticulum architecture, which mirror phenotypes caused by ribosome depletion. Lamin dysfunction also lowers nucleolar fibrillarin levels and ribosome abundance, revealing a nucleolar-ribosomal axis that transmits nuclear defects to the cytoplasm. Loss of the redundant LEM-domain proteins emr-1 and lem-2 phenocopied lamin mutants, indicating that cytoplasmic disorganization is a shared hallmark of EDMD. These findings connect nuclear architecture to whole-cell biophysics and suggest therapeutic strategies aimed at restoring ribosome function.

PMID:
42647638
Bibliographic data and abstract were imported from PubMed on 27 Aug 2026.

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