Cellular Basis of Laminopathies


The nuclear lamina is the main architectural component of a eukaryotic nucleus. More than an inert scaffold, the lamina is essential for maintaining proper nuclear organisation, epigenetic composition, transcriptional regulation and cell cycle progression. Mutations within lamin genes lead to a wide range of diseases known as laminopathies, among which the striking premature aging disease Hutchinson–Gilford progeria syndrome (HGPS) is the most well known. Studies regarding the cellular basis of laminopathies have advanced our knowledge of the nuclear lamina and yielded remarkable insights into the process of normal human aging. Understanding the molecular mechanisms responsible for disease manifestations has also led to the development of novel therapeutic strategies to address lamina‐related diseases. Ultimately, scientists and clinicians seek to provide treatment options to laminopathy patients to alleviate symptoms and perhaps to cure these diseases in the future.

Key Concepts:

  • Mutations in genes encoding lamin proteins lead to a wide range of diseases known as laminopathies.

  • The nuclear lamina plays essential roles in maintaining nuclear architecture, chromatin organisation, cellular differentiation and gene expression.

  • Studies of the molecular mechanisms underlying laminopathies have led to advances in the understanding of lamin structure and function.

  • Progerin, the mutant form of lamin A expressed in Hutchinson–Gilford progeria syndrome, is also present in normal individuals, albeit at a low level.

  • Recent advances have led to the development of noval therapeutic options for patients suffering from HGPS.

Keywords: nuclear lamina; lamins; laminopathies; muscular dystrophy; Hutchison–Gilford progeria syndrome; epigenetics; farnesylation; morpholino

Figure 1.

Lamin processing. Blue and black lines indicate different amino acid sequences.



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Cao, Kan(Jul 2012) Cellular Basis of Laminopathies. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022533]