Do fragments of the neural cell adhesion molecule NCAM with or without attached polysialic acid differentially regulate transcription?

• Applicant: Professorin Dr. Melitta Schachner
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Molecular and Cellular Neurology and Neuropathology
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250721355

The aims of the proposed studies are the analysis of the functional roles of the transmembrane neural cell adhesion molecule NCAM and its associated glycan polysialic acid (PSA) in regulating transcription. In preliminary experiments we showed that function-triggering antibodies against NCAM elicit changes in the expression pattern of genes and that proteolytic NCAM fragments reach the nucleus. These NCAM fragments comprise not only the intracellular, but remarkably also the transmembrane and part of the extracellular domains. The hypothesis is that transcription of genes is different in the presence or absence of fragment-associated PSA due to the different association of PSA-carrying and -lacking NCAM fragments with transcription factors or chromatin-associated molecules. We propose that PSA-modulated transcriptional regulation depends on the differentiation state of cells - with PSA being characteristic of more immature neurons. We also propose that transcriptional regulation by PSA-carrying and -lacking NCAM fragments is different from that induced by the known signal transduction pathways. The differentially transcribed genes will be identified and validated at the mRNA and protein levels, and their functions will be analyzed via established cell biological methods in vitro. These experiments should allow first insights into the functional potential of glycans attached to adhesion molecule fragments in the nucleus.

• DFG Programme: Research Grants