PT - JOURNAL ARTICLE AU - Emmanuel Brouillet AU - Alain Trembleau AU - Damien Galanaud AU - Michel Volovitch AU - Colette Bouillot AU - Cécile Valenza AU - Alain Prochiantz AU - Bernadette Allinquant TI - The Amyloid Precursor Protein Interacts with G<sub>o</sub> Heterotrimeric Protein within a Cell Compartment Specialized in Signal Transduction AID - 10.1523/JNEUROSCI.19-05-01717.1999 DP - 1999 Mar 01 TA - The Journal of Neuroscience PG - 1717--1727 VI - 19 IP - 5 4099 - http://www.jneurosci.org/content/19/5/1717.short 4100 - http://www.jneurosci.org/content/19/5/1717.full SO - J. Neurosci.1999 Mar 01; 19 AB - The function of the β-amyloid protein precursor (βAPP), a transmembrane molecule involved in Alzheimer pathologies, is poorly understood. We recently reported the presence of a fraction of βAPP in cholesterol and sphingoglycolipid-enriched microdomains (CSEM), a caveolae-like compartment specialized in signal transduction. To investigate whether βAPP actually interferes with cell signaling, we reexamined the interaction between βAPP and GoGTPase. 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 βAPP epitope, reduces high-affinity Go GTPase activity. This inhibition is specific of Gαo and is reproduced, in the absence of 22C11, by the addition of the βAPP C-terminal domain but not by two distinct mutated βAPP C-terminal domains that do not bind Gαo. This inhibition of Gαo GTPase activity by either 22C11 or wild-type βAPP cytoplasmic domain suggests that intracellular interactions between βAPP and Gαo 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 Gαo and βAPP in CSEM. We show that inhibition of basal Gαo GTPase activity also occurs within CSEM and correlates with the coimmunoprecipitation of Gαo and βAPP. The regulation of Gαo GTPase activity by βAPP in a compartment specialized in signaling may have important consequences for our understanding of the physiopathological functions of βAPP.