AMYLOID PRECURSOR PROTEIN IN CORTICAL-NEURONS - COEXISTENCE OF 2 POOLS DIFFERENTIALLY DISTRIBUTED IN AXONS AND DENDRITES AND ASSOCIATION WITH CYTOSKELETON

Embryonic cortical neurons in culture contain transmembrane amyloid pr ecursor protein (APP) capable of associating with the detergent-insolu ble cytoskeleton through interactions requiring the presence of its C- terminal. These transmembrane APPs are not detectable at the surface o f living cells. When neurons are fixed with paraformaldehyde alone, AP P is mainly visualized close to the membrane of the axon and cell body of 40% of neurons, with virtually no dendritic staining. Membrane per meabilization with detergent or methanol extends APP immunostaining to 100% of the cells and to all compartments, including the dendrites. T aken together, these results suggest that APP in embryonic neurons is present in two compartments, one more readily detectable in some axons and cell bodies and the other distributed throughout all neurons. The axonal and somatic pool of APP detectable after paraformaldehyde fixa tion alone is highly and rapidly augmented after exposure to calcium i onophores. We propose that calcium entry increases the amount of axona l APP close to the cell surface, but that the stabilization of the pro tein at the cell surface and its subsequent secretion require further physiological stimuli.