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Lamins: building blocks or regulators of gene expression?

Key Points

  • Lamins are members of the intermediate filament (IF) superfamily and are classified as type V IFs. However, the structure of lamin genes indicates that they were possibly the evolutionary pregenitors of this metazoan family.

  • Lamins form a filamentous cage at the nuclear envelope that is called the lamina. This structure has load-bearing properties, which provide strength to and determine the size and shape of the nucleus.

  • Lamins have several functions in the nucleus, including the recruitment of integral membrane proteins to the inner nuclear envelope and organizing the distribution of nuclear pore complexes. Lamins also have fundamental roles in DNA replication and transcription.

  • Mutations in the lamin genes have been shown to be the cause of a wide range of genetic diseases. The tissue-specific phenotypes that are associated with each disease indicate that lamins have a complex domain structure that enables them to interact with several different binding partners.

  • Recent studies indicate that lamins might have essential roles in the development of germline tissues, and this has apparently resulted in the evolution and expression of germline-specific lamins in vertebrates.

  • Future studies in this rapidly moving field might finally show how structural elements in the nucleus control gene expression.

Abstract

Intermediate filament (IF) proteins are the building blocks of cytoskeletal filaments, the main function of which is to maintain cell shape and integrity. The lamins are thought to be the evolutionary progenitors of IF proteins and they have profound influences on both nuclear structure and function. These influences require the lamins to have dynamic properties and dual identities — as building blocks and transcriptional regulators. Which one of these identities underlies a myriad of genetic diseases is a topic of intense debate.

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Figure 1: Organization of lamina filaments at the inner nuclear envelope.
Figure 2: Generalized structure of cytoplasmic intermediate filament proteins compared with lamins.
Figure 3: Model for a possible interaction between Nup153 and the lamins that anchor nuclear pore complexes in the nuclear membrane.
Figure 4: Lamin interactions at the inner nuclear membrane.

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Acknowledgements

The author would like to thank the Association for International Cancer Research, Against Bowel Cancer, the Muscular Dystrophy Campaign and the Wellcome Trust for grants that support the research in his laboratory.

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DATABASES

FlyBase

lamin Dm0

InterPro

CaaX box

IF

LocusLink

Face1/Ste24

LMNA

Lmna

OMIM

Charcot–Marie–Tooth disorder

dilated cardiomyopathy

Emery–Dreifuss muscular dystrophy

familial partial lipodystrophy

mandibuloacral dysplasia

Swiss-Prot

emerin

Gcl

GFP

lamins A/C

lamin B1

lamin B3

Lamin C

Lamin Dm0

Liii

MAN1

Nup153

Oct1

Tpα

Tpβ

WormBase

lmn-1

LMN-1

UNC-84

Glossary

METAZOA

A major division of the animal kingdom. It includes all animals except the Protozoa and Parazoa.

RNA INTERFERENCE

The process by which an introduced double-stranded RNA specifically silences the expression of genes through degradation of their cognate mRNAs.

TENSEGRITY ELEMENT

A lightweight load-bearing structure that can re-adopt its initial shape after deformation.

NUCLEAR BODY

A structure of defined size in the nucleus that is identifiable by immunofluorescence or electron microscopy, and contains all of the enzymes required for a specific metabolic function (for example, RNA splicing).

PERIPHERAL HETEROCHROMATIN

Heterochromatin that is physically linked to the nuclear envelope.

RNA POLYMERASE II

A eukaryotic enzyme that synthesizes mRNA precursors.

POU DOMAIN PROTEINS

A conserved family of transcription regulators that contain the sequence motif Pit–Oct–Unc.

RNA SPLICING-FACTOR SPECKLE

A nuclear body that acts as a reservoir for RNA splicing factors.

GEODESIC DOME

An architectural device, invented by Buckminster Fuller, in which icosahedral structures are used to enclose spaces in a dome.

IMMUNOGLOBULIN DOMAIN FAMILY

A family with structural similarity to immunoglobulin, as defined by the presence and organization of β-sheets and β-strands.

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Hutchison, C. Lamins: building blocks or regulators of gene expression?. Nat Rev Mol Cell Biol 3, 848–858 (2002). https://doi.org/10.1038/nrm950

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