A protein kináz D (PKD) mutációjának hatása a hippokampális szinapszisok szerkezetére

Abstract

Protein kinase D (PKD) is a serine-threonine kinase which can be found in a variety of cell types at various subcellular locations and it has a wide substrate specificity. Consequently, it is implicated in the regulation of a remarkable array of fundamental biological processes, such as transcription, cell proliferation and differentation, Golgi vesicle fission and transport, cell motility, immune signaling, survival after oxidative stress, inflammation, cardiac hypertrophy and various cancers. In neuronal cells, PKD plays an important role in cell polarity and development and arborization of dendrites. However, there is no data avaible on PKD functions in synapses. We studied the morphological changes in dendritic spines of pyramidal cells in the hippocamapl CA1 region, caused by the suspension of PKD function in kinase dead (kd) PKD-EGFP transgenic mice. We made sections from the brains of the animals, and then we visualized the kdPKD-EGFP protein expressing neurons by anti-GFP peroxidase immunohistochemistry. Subsequently, we examined the areas containig immunolabelled pyramidal cells in transmission electron microscope. We measured the postsynaptic profile areas, perimeters, profile circularity and postsynaptic density (PSD) lenghts and compared them to data collected from wild type (WT) animals. We found that the mean synaptic profile areas, perimeters and PSD lenghts were significantly decreased in transgenic animals compared to WT mice. In addition, the correlation between spine size and PSD lenght was markedly decreased in kdPKD mice. Thus we suggest that normal PKD activity is required for the optimal regulation of synaptic morphology. PKD likely controls the synaptic morphology through regulating the spine cytoskeleton (spinoskeleton), since various actin binding proteins (ABPs) are responsible for maintainig the spinoskeletal structure and PKD is known to phosphorilate many of these proteins, and cosequently has an influence on their functions.