Tài liệu Báo cáo khoa học: The nuclear lamina Both a structural framework and a platform for genome

MINIREVIEW

The nuclear lamina

Both a structural framework and a platform for genome

organization

Joanna M. Bridger1

, Nicole Foeger2

, Ian R. Kill1 and Harald Herrmann3

1 Centre for Cell and Chromosome Biology, Division of Biosciences, Brunel University, London, UK

2 Institute for Medical Biochemistry, Vienna Biocenter, Austria

3 Functional Architecture of the Cell, German Cancer Research Center (DKFZ), Heidelberg, Germany

Evolution of the intermediate filament

protein family

The nuclear lamina is a complex ensemble of proteins

that connects the inner nuclear membrane to chroma￾tin, and thus creates a link from the cytoplasm to the

genome. The nuclear lamina has received much atten￾tion recently, because presently 220 mutations have

been discovered within one of the constituent polypep￾tides, lamin A⁄ C, and these have been demonstrated

to be the cause of a number of severe human diseases,

termed laminopathies (for a recent review see [1]).

Moreover, their down-regulation is associated with

specific cancers, such as lymphoma and leukaemia [2],

and lung cancer [3].

In contemporary metazoan cells the lamina is com￾prised of fibrous polypeptides of the intermediate

filament (IF) protein family, one type in lower phyla

like cnidaria or nematodes and four major forms in

mammals, designated A-type (lamin A and lamin C)

and B-type (lamin B1 and lamin B2), in addition to an

increasing number of associated proteins [4]. Lamins

were originally isolated from the high salt⁄ detergent￾insoluble fractions of nuclear envelopes derived from

rat liver and named according to their apparent

molecular mass during SDS ⁄ PAGE [5]. Moreover,

B-type lamins are acidic and A-type lamins are basic,

as revealed by isoelectric focusing in conventional two￾dimensional polyacrylamide gel electrophoresis [6].

Molecular cloning as well as their appearance in the

Keywords

chromosomal organization; fluorescence

in situ hybridization; intermediate filaments;

lamins; nuclear envelope

Correspondence

H. Herrmann, B065 Functional Architecture

of the Cell, German Cancer Research

Center (DKFZ), Im Neuenheimer Feld 580,

D-69120 Heidelberg, Germany

Fax: +49 62214 23519

Tel: +49 62214 23512

E-mail: [email protected]

(Received 26 February 2006, accepted 8

January 2007)

doi:10.1111/j.1742-4658.2007.05694.x

The inner face of the nuclear envelope of metazoan cells is covered by a thin

lamina consisting of a one-layered network of intermediate filaments inter￾connecting with a complex set of transmembrane proteins and chromatin

associating factors. The constituent proteins, the lamins, have recently gained

tremendous recognition, because mutations in the lamin A gene, LMNA, are

the cause of a complex group of at least 10 different diseases in human, inclu￾ding the Hutchinson–Gilford progeria syndrome. The analysis of these dis￾ease entities has made it clear that besides cytoskeletal functions, the lamina

has an important role in the ‘behaviour’ of the genome and is, probably as a

consequence of this function, intimately involved in cell fate decisions. Fur￾thermore, these functions are related to the involvement of lamins in organ￾izing the position and functional state of interphase chromosomes as well as

to the occurrence of lamins and lamina-associated proteins within the nucleo￾plasm. However, the structural features of these lamins and the nature of the

factors that assist them in genome organization present an exciting challenge

to modern biochemistry and cell biology.

Abbreviations

IF, intermediate filament; LAP, lamina-associated protein; LBR, lamin B receptor.

1354 FEBS Journal 274 (2007) 1354–1361 ª 2007 The Authors Journal compilation ª 2007 FEBS