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http://purl.uniprot.org/citations/10024358http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10024358http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10024358http://www.w3.org/2000/01/rdf-schema#comment"The function of the beta-amyloid protein precursor (betaAPP), a transmembrane molecule involved in Alzheimer pathologies, is poorly understood. We recently reported the presence of a fraction of betaAPP in cholesterol and sphingoglycolipid-enriched microdomains (CSEM), a caveolae-like compartment specialized in signal transduction. To investigate whether betaAPP actually interferes with cell signaling, we reexamined the interaction between betaAPP and Go GTPase. In strong contrast with results obtained with reconstituted phospholipid vesicles (Okamoto et al., 1995), we find that incubating total neuronal membranes with 22C11, an antibody that recognizes an N-terminal betaAPP epitope, reduces high-affinity Go GTPase activity. This inhibition is specific of Galphao and is reproduced, in the absence of 22C11, by the addition of the betaAPP C-terminal domain but not by two distinct mutated betaAPP C-terminal domains that do not bind Galphao. This inhibition of Galphao GTPase activity by either 22C11 or wild-type betaAPP cytoplasmic domain suggests that intracellular interactions between betaAPP and Galphao could be regulated by extracellular signals. To verify whether this interaction is preserved in CSEM, we first used biochemical, immunocytochemical, and ultrastructural techniques to unambiguously confirm the colocalization of Galphao and betaAPP in CSEM. We show that inhibition of basal Galphao GTPase activity also occurs within CSEM and correlates with the coimmunoprecipitation of Galphao and betaAPP. The regulation of Galphao GTPase activity by betaAPP in a compartment specialized in signaling may have important consequences for our understanding of the physiopathological functions of betaAPP."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.org/dc/terms/identifier"doi:10.1523/jneurosci.19-05-01717.1999"xsd:string
http://purl.uniprot.org/citations/10024358http://purl.org/dc/terms/identifier"doi:10.1523/jneurosci.19-05-01717.1999"xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Prochiantz A."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Prochiantz A."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Allinquant B."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Allinquant B."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Bouillot C."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Bouillot C."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Brouillet E."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Brouillet E."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Galanaud D."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Galanaud D."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Trembleau A."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Trembleau A."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Valenza C."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Valenza C."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Volovitch M."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/author"Volovitch M."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/name"J. Neurosci."xsd:string
http://purl.uniprot.org/citations/10024358http://purl.uniprot.org/core/name"J. Neurosci."xsd:string