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 precursor protein (APP) is distributed in two pools. Whereas the first pool is present in all cell compartments, the second pool is highly enriched in the axon and cell body. In an earlier study we demonstrated that this second pool, referred to as axonal-APP (Ax-APP), is present in the vicinity of the plasma membrane and colocalizes only partially with clathrin (Allinquant, B., Moya, K.L., Bouillot, C., and Prochiantz, A. (1994) J. Neurosci. 14, 6842-6854). In this report, using immunocytochemical and fractionation techniques we demonstrate that Ax-APP is present in microdomains enriched in the glypiated glycoprotein F3. The F3/Ax-APP microdomains are resistant to nonionic detergents and sediment at low density on a sucrose gradient. The two latter properties are reminiscent of those of caveolae, a type of plasmalemmal vesicle found in several cell types, but not previously described in the nervous 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 leading to the production of the amyloidogenic betaA4 peptide.
Bouillot
C
C
CNRS, Ecole Normale Supérieure, Paris, France.
Prochiantz
A
A
Rougon
G
G
Allinquant
B
B
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000096:biosynthesis*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002454:Cell Differentiation; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D002966:Clathrin / Q000032:analysis; D004285:Dogs; D005333:Fetus; D007150:Immunohistochemistry; D007668:Kidney; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity; D015388:Organelles / Q000378:metabolism / Q000648:ultrastructure; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D002966:Clathrin; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase