Servicio de Información Comunitario sobre Investigación y Desarrollo - CORDIS

Expression and lateral topography of neural membrane proteins

The project concerns lateral organization of membrane proteins on surfaces of developing nerve cells exposed to effects of neuroplasticity and cytoskeletal disruption. The work focused on mechanisms that relate the expression and lateral topography of neural membrane proteins (in particular cell adhesion molecules), and the cytoskeleton-dependent structure of synaptic elements (in particular dendritic spines and presynaptic boutons) to inter-neural communication that underlies the process of learning and memory formation. In the domestic chick forebrain, the polysialic acid enriched, and the main isoforms of neuron cell adhesion molecule (N-CAM) are not distributed purely at random in synaptic neuropil, but tend to cluster and colocalise. At the same time, these molecules tend to accumulate specifically towards the edges of synaptic contacts, and there is a significantly increased proportion of synaptic contacts exhibiting N-CAM epitopes labelled immunocytochemically at the electron microscope level within 5-6 h after a passive avoidance training. These data suggest that there is a period after learning experience (in the chick) when expression of N-CAMs in synaptic membranes almost doubles, and that events at active zone edges may play a specific role in mechanisms of synaptic adhesion.

At the level of cytoskeleton, the disruption of microtubules and neurofilaments in cultured hippocampal cells was shown to cause a significant increase in the density of N-CAM epitopes on nerve cell surfaces detected using immunoelectron microscopy. Regarding the functioning of synaptic transmission it was demonstrated that selective removal of polysialic acid (PSA) from N-CAM extracellular domains blocked induction of long-term potentiation without affecting other synaptic parameters. In general, the results obtained elucidate important molecular mechanisms that regulate the development, establishment and functional modification of nerve cell contacts through the expression and lateral re-arrangement of 'recognition' molecules (in particular cell adhesion molecules) associated with the sites of synaptic contacts.


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