Functional characterization of newly identified inserted membrane proteins of the nuclear envelope

• Antragstellerin: Dr. Anja Bubeck
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2004 bis 2006
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5444355

The nuclear envelope (NE) constitutes the interface between the nucleus and the cytoplasm. Notwithstanding its role in nuclear structure, increasing evidence indicates that the NE also is involved in regulation of cellular processes. Mutations in genes coding for proteins of the NE can cause a variety of diseases affecting striated muscle. How mutations in these genes, which are ubiquitously expressed lead to a tissue-specific manifestation of disease is not clear. Using comprehensive proteomic methods the Gerace laboratory has recently identified 67 previously uncharacterized integral proteins of the NE. This project will focus on the characterization of the products of a subset of these genes that are located in chromosomal regions linked to mutations causing several types of muscular dystrophies (MDs). We aim to functionally characterize some of these candidate genes with respect to their role in cell organization, function and muscle cell differentiation. To this end, expression of the candidate genes will be individually repressed in a cultured myoblast cell system, to screen for the effects of gene down-regulation on cell growth, nuclear and cytoplasmic organization and on muscle cell differentiation. This study will contribute to the understanding of the function of integral proteins of the NE in cells. The use of a muscle cell model allows further to investigate the function of candidate genes in muscle cell differentiation. This will provide insights into the mechanism by which NE proteins cause MDs and other diseases.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Kooperationspartner: Professor Dr. Larry Gerace