Drosophila as a Model for Studying the Roles of Lamins in Normal Tissues and Laminopathies

Nuclear processes are fundamental to the regulation of cellular, tissue, and organismal function, especially in complex multicellular systems. Central to these processes are lamins and lamin-associated proteins, which contribute to nuclear structure, gene expression, and chromatin organization. The discovery that mutations in genes coding for lamins and lamina-associated proteins give rise to rare disorders—collectively called laminopathies—has intensified interest in this field among cell biologists and medical scientists. While many practical and clinically relevant questions about phenotype development and potential treatments require mammalian models, key molecular mechanisms and interactions have also been effectively studied in both vertebrate and invertebrate systems. This review focuses on discussion of Drosophila lamins, their major properties, functions, interactions and post-translational modifications with comparison to mammalian lamins and discussion of the value of fly model in studies of lamins in muscle tissue development and function in comparison to mammalian lamin B-type and A/C type. In this part we have discussed the overall impact of lamin Dm and lamin C levels manipulations on overall phenotype and especially on larval and adult muscles. We have thoroughly discussed the conclusions which may have been drawn from experiments with overexpression of lamin C mutants mimicking lamin A laminopathy mutations. We have presented and discussed the suggestion that the mechanisms underlining the Drosophila muscle phenotype development are similar not only to human dystrophic laminopathies but also to typical human muscular dystrophy such as Duchenne muscular dystrophy and Hutchison Gilford Progeria syndrome. We suggest that activation of stress response contributes to the laminopathic phenotype detected in Drosophila. Finely, this review discusses in depth the lamin Dm and lamin C interactome and discrepancies between String-based interactome network and our map of interactomes based on manual verification of experimental data on Drosophila lamin interactions.