Analysis of Beta-Dystroglycan in Different Cell Models of Senescence

The functional diversity of ß-dystroglycan is attributable to its dual distribution, the plasma membrane, and the nucleus. In the plasma membrane, ß-DG is a component of the dystrophin-associated protein complex. In the nucleus, ß-DG assembles with the nuclear lamina and emerin. Recent findings indicate a role for ß-DG in senescence, as its knockout in C2C12 myoblasts induces genomic instability and promotes the senescent state. This study analyzed the behavior of ß-DG in three distinct models of senescence: chronologically aged fibroblasts, sodium butyrate (NaBu)-induced senescent fibroblasts, and fibroblasts from a Hutchinson¿Gilford progeria syndrome (HGPS) patient. ß-DG was found mainly in the nucleus in all the senescent cell types, with a certain mislocalization to the cytoplasm in HGPS and NaBu-treated fibroblasts. Furthermore, the full-length ß-DG (43 kDa) and the cleaved intracellular domain (ICD; ~26 kDa) were identified. The ICD level increased in aged fibroblasts, but its yield was poor or virtually nonexistent in NaBU-induced and HGPS fibroblasts, respectively. Remarkably, ß-DG was sequestered by progerin in HGPS cells, hindering its interaction with lamin A. In summary, the observed alterations in ß-DG may be associated with the senescent state, and such findings will serve for future studies aimed at elucidating its role in senescence. © 2025 by the authors.

Analysis of Beta-Dystroglycan in Different Cell Models of Senescence Academic Article in Scopus