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Programming cells: The importance of the envelope
Date:2/1/2013

nuclear membrane as clamps lamin A/C, and the so-called lamin-B receptor (LBR), which itself binds to B type lamins.

Normally the two components are used sequentially for this purpose. "In the course of differentiation, there is a switch from the LBR to lamin A/C, and there is always a least one type of tether available for attachment of heterochromatin to the nuclear periphery. But if both are missing, the inactive heterochromatin recoils like a severed elastic band and collapses in the center of the nucleus," explains Leonhardt. Moreover, the switch seems to be a fundamental principle of genome organization and cell differentiation in mammalian cells, as the researchers concluded from the study of 39 species and the analysis of diverse tissue types in nine genetic strains of mice.

Prospects for targeted therapies

Lamin proteins not only have a structural function but also have an impact on gene regulation. Thus LBR binds B type lamins and regulates stem-cell populations by promoting the expression of genes that are important for the proliferation of rapidly dividing stem cells. The lamin A/C gene on the other hand codes for a structural component of the nuclear envelope, and regulates cellular differentiation programs like e.g. the expression of muscle-specific genes in muscle cells. Mutations in this gene result in so-called laminopathies rare genetic diseases that are associated with a broad spectrum of clinical symptoms, including muscular dystrophy and progeria, a premature aging syndrome.

Joffe and Solovei suspect that mutations in lamin A/C affect the expression of specific genes during the maturation and differentiation of cells, with deleterious results for their function and for tissue integrity. This notion could explain the highly diverse and complex symptoms seen in patients with mutations in the lamin A/C gene - and it could open routes to the design of targeted therapies for laminopathies.

The new find
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Contact: Luise Dirscherl
dirscherl@lmu.de
0049-892-180-2706
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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