I continue to evaluate factors affecting the internalization, degradation and transport of lectin-HRP conjugates in the central and peripheral nervous system of rats. Such factors probably also regulate the interneuronal transfer of these probes. The progress in the past year has resulted in the development of methods which permit the immunochemical detection of species of lectin-HRP conjugates, such as wheat germ agglutinin conjugated to HRP (WGHRP), following internalization and transport in the nervous system in rats. These methods have shown that WGHRP is rapidly degraded by neurons as the lectin-HRP conjugates accumulate in neuronal perikarya following retrograde transport. The relative resistance of WGHRP to degradation following internalization at the level of the neuronal perikaryon versus the axon terminals of a neuron may account for the ability of WGHRP to undergo interneuronal transfer following orthograde, but not retrograde, transport to the visual artex. I will determine the forms of WGHRP which are internalized by retinal ganglion cells and compare them with the species of WGHRP which arrive at the axon terminals of reinal ganglion cells following orthograde transport in the two neuronatomical systems used to study this important phenomenon. In the coming year these studies will be extended using immunochemical methods to identify species of WGHRP which reach the axon terminals of neurons. After reaching the axon terminals of retinal ganglion cells, I have shown that WGHRP (and/or its degradative products) is released to undergo another cycle of internalization and orthograde transport by these same neurons. Comparisons will be made with transported native HRP since native HRP does not undergo interneuronal transfer. These studies should enable me to specifically identify the form or forms in which WGHRP exists as it is released from retinal ganglion cell axon terminals for uptake by other neurons in the superior colliculus and lateral geniculate body. These studies will provide insights into the mechanisms which determine or regulate the interneuronal transfer of exogenous proteins in the nervous system.
Showing the most recent 10 out of 13 publications