Nuclear lamins: laminopathies and their role in premature ageing.
It has been demonstrated that nuclear lamins are important proteins in maintaining cellular as well as nuclear integrity, and in maintaining chromatin organization in the nucleus. Moreover, there is growing evidence that lamins play a prominent role in transcriptional control. The family of laminopathies is a fast-growing group of diseases caused by abnormalities in the structure or processing of the lamin A/C (LMNA) gene. Mutations or incorrect processing cause more than a dozen different inherited diseases, ranging from striated muscular diseases, via fat- and peripheral nerve cell diseases, to progeria. This broad spectrum of diseases can only be explained if the responsible A-type lamin proteins perform multiple functions in normal cells. This review gives an overview of current knowledge on lamin structure and function and all known diseases associated with LMNA abnormalities. Based on the knowledge of the different functions of A-type lamins and associated proteins, explanations for the observed phenotypes are postulated. It is concluded that lamins seem to be key players in, among others, controlling the process of cellular ageing, since disturbance in lamin protein structure gives rise to several forms of premature ageing.
Broers
J L V
JL
Department of Molecular Cell Biology, University of Maastricht, Research Institutes CARIM, GROW, and EURON, The Netherlands.
Ramaekers
F C S
FC
Bonne
G
G
Yaou
R Ben
RB
Hutchison
C J
CJ
D019588:Aging, Premature / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D034882:Lamins / Q000502:physiology*; D034881:Nuclear Lamina / Q000473:pathology*
D034882:Lamins