Axonal Amyloid Precursor Protein Expressed by Neurons in Vitro Is Present in a Membrane Fraction with Caveolae-like Properties (*)
- From the From CNRS, URA 1414, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris Cedex 05, France and
- CNRS, UPR 9943, Case 907, Université de Luminy, 13288 Marseille Cedex 09, France
- §To whom correspondence should be addressed: Tel.: 33-1-44-32-39-26; Fax: 33-1-44-32-39-88; prochian{at}wotan.ens.fr.
Abstract
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 βA4 peptide.
Footnotes
-
↵* This work was supported by CNRS, Ecole Normale Supérieure and grants from the European Community (BIO2-CT93-0012), Direction des Recherches et Etudes Techniques (92-141) and INSERM (CRE 930807 and 920812). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- APP
-
amyloid precursor protein
- Ax-APP
-
axonal APP
- MDCK
-
Madin-Darby canine kidney cells
- PBS
-
phosphate-buffered saline
- PAGE
-
polyacrylamide gel electrophoresis
- Mes
-
4-morpholineethanesulfonic acid
- PI
-
phosphatidylinositol
- PLC
-
phospholipase C
- GPI
-
glycosylphosphatidylinositol.
-
- Received May 9, 1995.
- Revision received December 18, 1995.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
