A striking feature of the postsynaptic membrane in the neuromuscular junction and in electric tissue of electric rays is the very high density of acetylcholine receptors. This project seeks to identify possible mechanisms by which such a localized high density is stabilized. Postsynaptic membranes isolated from electric tissue are known to contain a major peripheral membrane protein (the so-called 43K protein) in addition to the receptor protein. I have shown by ultrastructural techniques that the 43K protein is probably a component of the cytoplasmic surface. It seems to lie roughly in a layer, parallel to the plane of the membrane and near to or associated with the cytoplasmic ends of the receptor molecules. Clearly, such a structure could have as its function the stabilization of the receptor arrays, possible by direct association with the receptor. In the coming year, I will study the structure and biochemistry of the 43K protein in its native state. I will attempt to find conditions for its removal from the membrane under which the extensive aggregation thus far observed is avoided, so that its minimum native size and self-association properties can be studied. By ultrastructural means, I will attempt to determine whether the 43K protein forms a supramolecular assembly in its membrane-bound state, and, if so, to determine the size and structure of the assembly. Present evidence indicates that the 43K protein as extracted from the membrane consists of 2 proteins. If this is confirmed, I will develop ways by which the two proteins can be separated in native forms. The association of the two will be studied. In additional studies, receptor movements in the postsynaptic membrane of chick or mouse endplates will be followed at the ultrastructural level.
Showing the most recent 10 out of 14 publications
