Laminopathies and the long strange trip from basic cell biology to therapy.
The main function of the nuclear lamina, an intermediate filament meshwork lying primarily beneath the inner nuclear membrane, is to provide structural scaffolding for the cell nucleus. However, the lamina also serves other functions, such as having a role in chromatin organization, connecting the nucleus to the cytoplasm, gene transcription, and mitosis. In somatic cells, the main protein constituents of the nuclear lamina are lamins A, C, B1, and B2. Interest in the nuclear lamins increased dramatically in recent years with the realization that mutations in LMNA, the gene encoding lamins A and C, cause a panoply of human diseases ("laminopathies"), including muscular dystrophy, cardiomyopathy, partial lipodystrophy, and progeroid syndromes. Here, we review the laminopathies and the long strange trip from basic cell biology to therapeutic approaches for these diseases.
Worman
Howard J
HJ
Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. hjw14@columbia.edu
Fong
Loren G
LG
Muchir
Antoine
A
Young
Stephen G
SG
D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology* / Q000628:therapy; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D034921:Lamin Type B / Q000235:genetics; D008060:Lipodystrophy / Q000209:etiology* / Q000628:therapy; D008565:Membrane Proteins / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D009136:Muscular Dystrophies / Q000209:etiology* / Q000628:therapy; D009154:Mutation; D009685:Nuclear Envelope / Q000502:physiology; D034881:Nuclear Lamina / Q000502:physiology*; D011371:Progeria / Q000209:etiology* / Q000628:therapy; D011499:Protein Processing, Post-Translational
C494847:LMNA protein, human; D034904:Lamin Type A; D034921:Lamin Type B; D008565:Membrane Proteins; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human