Generation and Utilization of Monoclonal Antibodies as Probes of Slow NGF Receptor Structure and Function

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Intercellular biochemical communication is a ubiquitous feature in biology serving to mediate an enormous range of regulatory functions. In vertebrate nervous systems, targets of innervation secrete proteins known as neurotrophic factors, which are subsequently received by the innervating neuron. Acquisition of sufficient neurotrophic factor by individual innervating neurons is essential for the proper development and maintenance of the nervous system. Interruption of the flow of neurotrophic factor from the target to the neurons result in the rapid neuronal destruction of the affected region. In Dr. Feinstein's project, he will examine the molecular mechanisms by which Nerve Growth Factor (NGF), the best understood among the neurotrophic factors, mediates its action upon responsive neuronal cells. NGF action is known to be initiated by the interaction of NGF with "slow" (also known as "high affinity") NGF receptors located in the neuronal plasma membrane. He will first utilize a variety of immunological strategies to generate novel molecular probes. Then, he will use these probes as tools to investigate the molecular composition of the slow NGF receptors as well as the functions mediated by the slow NGF receptors. These studies should markedly contribute to our understanding of neurotrophic factor action and the development and maintenance of the nervous system.*** //