2025/07/01 by Stan W. van Wijk, Puck Vree, Fabries G. Huiskes +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Cardiomyopathy and Myosin Studies #Insect Resistance and Genetics #Nuclear Structure and Function
paper · pdf · doi:10.1242/dmm.052424
openalex publication_date 2025/07/01 · openalex created_date 2025/07/03 · openalex updated_date 2026/08/01
Atrial fibrillation (AF), the most common progressive cardiac arrhythmia, is associated with serious complications such as stroke and heart failure. Although common risk factors underlie AF onset, in 15% of the affected population, AF may have a genetic cause. Here, we investigated how LMNA variants cause cardiac arrhythmicity. Drosophila melanogaster strains were generated possessing the analogous variants in the Drosophila orthologue of human lamin A/C (LMNA), Lamin C (LamC). Heart wall movements in prepupae were recorded before (BTP) and after (ATP) tachypacing. ATP, flies expressing wild-type LamC, and the variants ΔN and p.R205W showed a significant reduction in heart rate (HR), but the arrhythmia index (AI) was not affected, compared to BTP. By contrast, those expressing p.N210K and p.R264Q showed a significant reduction in HR and increased AI, compared to BTP. p.N210K- and p.R264Q-expressing prepupae showed contrasting effects after pharmacological intervention with microtubule stabilizer taxol. Taxol attenuated the arrhythmogenicity in p.N210K-expressing prepupae, but aggravated it in p.R264Q-expressing prepupae. These findings suggest that different lamin variants trigger distinct molecular pathways that drive arrhythmogenic effects in Drosophila.