A and B type lamins, the nuclear intermediate filaments, have been identified as structural platforms that interconnect signals from the extra-cellular environment and cytoskeleton to chromatin remodeling and activity. Such a role of master regulators of the cell may explain the occurrence of more than 15 diseases linked to LMNA or LMNB1/2 genes. Noteworthy, the number of diseases associated with mutations in LMNA surpasses that of any other human gene. Diseases linked to lamins or their partner proteins at the nuclear envelope, collectively known as laminopathies, include muscular dystrophies, cardiomyopathy, lipodystrophies, neuropathies, developmental and progeroid syndromes. The study of pathogenetic mechanisms causing each laminopathy did not allow us to find a cure for most of the diseases, but it is shedding light on major mechanisms potentially affected in diseases and basic mechanisms of nuclear envelope/lamina remodeling upstream of cellular differentiation and cell and organism senescence. To recapitulate major advances in the field of laminopathies research means to mention that in the last ten years it has been discovered the role of prelamin A in cellular and organism aging, mostly based on prelamin A effects on chromatin dynamics, it has been identified the role of lamins and their binding partners as switches from the undifferentiated to the differentiated state, mostly in adult stem cells, it has been unraveled the role of the so called LINC complex, constituted by bridging molecules at the boundary between the nucleus and the cytoskeleton. In the context of neuromuscular disorders, data from our group have involved a new player in the crosstalk between the nuclear envelope and the cytoskeleton during the process of muscle differentiation. It has been discovered that nuclear positioning required to form mature muscle fibers is regulated through interplay of lamins and LINC complex molecules with pericentrin and have identified altered anchorage and misfunctioning of the centrosomal protein in muscular dystrophy. Finally, it has been reported that lamins are required to send signals out of the cells, playing unexpected roles at the systemic level. The relevance of these biological mechanisms to muscle differentiation and the potential perspectives for translational approaches will be presented.
Cellular dynamics regulated by lamins: focus on neuromuscular disorders
Giovanna Lattanzi
2014
Abstract
A and B type lamins, the nuclear intermediate filaments, have been identified as structural platforms that interconnect signals from the extra-cellular environment and cytoskeleton to chromatin remodeling and activity. Such a role of master regulators of the cell may explain the occurrence of more than 15 diseases linked to LMNA or LMNB1/2 genes. Noteworthy, the number of diseases associated with mutations in LMNA surpasses that of any other human gene. Diseases linked to lamins or their partner proteins at the nuclear envelope, collectively known as laminopathies, include muscular dystrophies, cardiomyopathy, lipodystrophies, neuropathies, developmental and progeroid syndromes. The study of pathogenetic mechanisms causing each laminopathy did not allow us to find a cure for most of the diseases, but it is shedding light on major mechanisms potentially affected in diseases and basic mechanisms of nuclear envelope/lamina remodeling upstream of cellular differentiation and cell and organism senescence. To recapitulate major advances in the field of laminopathies research means to mention that in the last ten years it has been discovered the role of prelamin A in cellular and organism aging, mostly based on prelamin A effects on chromatin dynamics, it has been identified the role of lamins and their binding partners as switches from the undifferentiated to the differentiated state, mostly in adult stem cells, it has been unraveled the role of the so called LINC complex, constituted by bridging molecules at the boundary between the nucleus and the cytoskeleton. In the context of neuromuscular disorders, data from our group have involved a new player in the crosstalk between the nuclear envelope and the cytoskeleton during the process of muscle differentiation. It has been discovered that nuclear positioning required to form mature muscle fibers is regulated through interplay of lamins and LINC complex molecules with pericentrin and have identified altered anchorage and misfunctioning of the centrosomal protein in muscular dystrophy. Finally, it has been reported that lamins are required to send signals out of the cells, playing unexpected roles at the systemic level. The relevance of these biological mechanisms to muscle differentiation and the potential perspectives for translational approaches will be presented.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
