AXONAL AMYLOID PRECURSOR PROTEIN EXPRESSED BY NEURONS IN-VITRO IS PRESENT IN A MEMBRANE-FRACTION WITH CAVEOLAE-LIKE PROPERTIES

In cortical neurons differentiating in vitro, transmembrane amyloid pr ecursor protein (APP) is distributed in two pools. Whereas the first p ool is present in all cell compartments, the second pool is highly enr iched in the axon and cell body. In an earlier study we demonstrated t hat this second pool, referred to as axonal-APP (Ax-APP), is present i n the vicinity of the plasma membrane and colocalizes only partially w ith clathrin (Allinquant, B., Moya, K. L., Bouillot, C., and Prochiant z, A. (1994) J. Neurosci. 14, 6842-6854). In this report, using immuno cytochemical and fractionation techniques we demonstrate that Ax-APP i s present in microdomains enriched in the glypiated glycoprotein F3. T he F3/Ax-APP microdomains are resistant to nonionic detergents and sed iment at low density on a sucrose gradient. The two latter properties are reminiscent of those of caveolae, a type of plasmalemmal vesicle f ound in several cell types, but not previously described in the nervou s system due to the absence of caveolin in neurons. The presence of Ax -APP in caveolae-like vesicles raises the possibility that APP serves as a transmembrane signaling molecule for GPI-linked glycoproteins. In addition, our data support new hypotheses on the endocytic pathways l eading to the production of the amyloidogenic beta A4 peptide.