The nuclear envelope, a key structure in cellular integrity and gene expression

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Curr Med Chem. 2007;14(11):1231-48.

The nuclear envelope, a key structure in cellular integrity and gene

expression.

Verstraeten VL, Broers JL, Ramaekers FC, van Steensel MA.

Department of Dermatology, University Hospital Maastricht, P.

Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, The Netherlands.

The envelope that encapsulates the cell nucleus has recently gained

considerable interest, as several clinical syndromes are linked to

mutations in its molecular components. Most disorders recognized so

far are caused by defects in the nuclear lamins, building blocks of

a filamentous network lining the nucleoplasmic side of the inner

nuclear membrane.

Nuclear lamins are the evolutionary precursors of cytoskeletal

intermediate filaments and associate in a head-to-tail manner into a

stable lamina at the nuclear periphery and into a more dispersed

structure in the nucleoplasm. Lamins have a scaffolding function for

several nuclear processes such as transcription, chromatin

organization and DNA replication, and maintain nuclear and cellular

integrity.

Mutations in the LMNA gene, encoding A-type lamins, can cause

cardiac and skeletal muscle disease, lipodystrophy and premature

ageing phenotypes. Hence, the integrity of the nuclear envelope

seems essential for longevity. Furthermore, the laminopathies

provide evidence that metabolism and ageing are as tightly linked in

humans as they are in model organisms such as C. elegans.

In this review, we elaborate on the structure and functions of

nuclear lamins, the spectrum of syndromes related to mutations in

nuclear envelope components and pathogenic concepts unifying these

disorders.