Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene

• DOI: 10.1242/jcs.114.24.4459
• Publication Date: 2021-04-26T00:33:08Z
• Authors: Corinne Vigouroux; Martine Auclair; Emmanuelle Dubosc...; Marcel Pouchelet; Jacqueline Capeau; Jean-Claude Courv...; Brigitte Buendia
• Keywords: Nuclear lamina; LMNA; Inner membrane; Nuclear membrane; Emerin; Progeria

Dunnigan-type familial partial lipodystrophy (FPLD), characterized by an abnormal body fat redistribution with insulin resistance, is caused missense heterozygous mutations in A-type lamins (lamins A and C). A- B-type are ubiquitous intermediate filament proteins that polymerize at the inner face of nuclear envelope. We have analyzed primary cultures skin fibroblasts from three patients harboring R482Q or R482W mutations. These cells were euploid able to cycle divide. subpopulation these had blebbing nuclei forming a peripheral meshwork, which was frequently disorganized. Inner membrane protein emerin, lamin-binding protein, strictly colocalized this meshwork. Cells lipodystrophic often other envelope defects, mainly consisting herniations deficient lamins, pore complexes, lamina-associated 2 beta, chromatin. The mechanical properties envelopes altered, as judged extensive deformations observed heat-shocked cells, low stringency extraction their components. structural alterations A/C mutations, same changes introduced human control ectopic expression mutated lamin A.