This research program is designed to localize two specific proteins within internal membrane systems of both the cell body and the nerve axon. Localization of these proteins will elucidate the involvement of the nerve cells' internal membrane systems in the packaging of proteins destined for different target areas of the surface membrane or extracellular space. The two target proteins to be studied are : 1) the Na+ - K+ ATPase; and 2) acetylcholinesterase (AChE). These proteins will be localized with the aid of specific antibody probes visualized by light and electron microscopy. These two proteins are important in regulating the electrical and chemical activities associated with communication between nerve cells. The membrane systems under study are both those of the cell body and of the axon. In the cell body, the membrane systems to be studied are involved in the biosynthesis and packaging of membrane proteins or secretion products. In the axon, there are at least three distinct membrane systems whose functions or relationship are not known at this time. Investigations into the biosynthesis and transport of these proteins are permitted by the recent production and characterization of specific antibodies to each that may be used as probes to label each using a combination of light and electron microscopic techniques. Ultimately, the activities of this research program will provide a map of the subcellular pathways along which differing molecular forms of two macromolecules, crucially involved in nerve impulse and synaptic transmission, are transported to their respective destinations and finally combined and inserted into their functional positions. This investigation, using specific probes for the distribution of each protein, will define the functional relationship between morphologically differing membrane systems of the axon. As a result of these studies we will gain a greater understanding of the cellular mechanisms which regulate the life cycle of these important macromolecules.***
