University of Cambridge > > Physics of Medicine (PoM) Seminar Series > Nuclear structural networks: The hardware for regulation of gene expression and stem cell fate

Nuclear structural networks: The hardware for regulation of gene expression and stem cell fate

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Lamins are intermediate filament (IF) proteins specialized to form two-dimensional networks at the inner nuclear membrane (INM) of every metazoan cell nucleus, as impressively seen in the giant cell nuclei of Xenopus laevis oocytes. The establishment of such regular and extended lamin fiber systems as well as their degree of connectivity is extensively regulated by factors within the INM , such as emerin and lamin B receptor (LBR). Thereby a structure is formed that has been called by Blobel and colleagues “the nuclear lamina”. Moreover, lamins coordinate interactions that occur specifically in somatic cells, i.e. the association of the nuclear envelope with components of interphase chromatin such as histones and the barrier-to-autointegration factor (BAF). Recently, mutations in lamin A have been demonstrated to cause a bewildering number of different human diseases such as Emery-Dreifuss muscular dystrophy (EDMD), cardiomyopathy and premature ageing. The various pathomechanisms may in part depend on structural changes of the nuclear envelope, however, they may also relate to the specific association with distinct signalling molecules, transcription factors and chromosomes. In addition, it has been hypothesized that a widespread A-type lamin system may functionally organize architecture within the cell nucleus. We have now established conditions to renature recombinant lamin A and generate homogenous complexes in order to analyze the potential interactions these molecules undertake to form fibrillar structures. Thereby we are also able to investigate at which level of organization wild-type and mutated lamin A molecules differ.

Harald Herrmann Group Functional Architecture of the Cell Division Molecular Genetics German Cancer Research Center (DKFZ) Heidelberg, Germany

This talk is part of the Physics of Medicine (PoM) Seminar Series series.

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