Laminopathies and the long strange trip from basic cell biology to therapy

J Clin Invest. 2009 Jul;119(7):1825-36. doi: 10.1172/JCI37679. Epub 2009 Jul 1.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiomyopathies / etiology*
  • Cardiomyopathies / therapy
  • Humans
  • Lamin Type A / genetics*
  • Lamin Type B / genetics
  • Lipodystrophy / etiology*
  • Lipodystrophy / therapy
  • Membrane Proteins / genetics
  • Metalloendopeptidases / genetics
  • Muscular Dystrophies / etiology*
  • Muscular Dystrophies / therapy
  • Mutation*
  • Nuclear Envelope / physiology
  • Nuclear Lamina / physiology*
  • Progeria / etiology*
  • Progeria / therapy
  • Protein Processing, Post-Translational

Substances

  • LMNA protein, human
  • Lamin Type A
  • Lamin Type B
  • Membrane Proteins
  • lamin B1
  • lamin B2
  • Metalloendopeptidases
  • ZMPSTE24 protein, human