PMID- 10024358
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20191023
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 5
DP  - 1999 Mar 1
TI  - The amyloid precursor protein interacts with Go heterotrimeric protein within a
      cell compartment specialized in signal transduction.
PG  - 1717-27
AB  - 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.
FAU - Brouillet, E
AU  - Brouillet E
AD  - Centre National de la Recherche Scientifique, Unite de Recherche Associee 1414,
      Ecole Normale Superieure, 75230 Paris Cedex 05, France.
FAU - Trembleau, A
AU  - Trembleau A
FAU - Galanaud, D
AU  - Galanaud D
FAU - Volovitch, M
AU  - Volovitch M
FAU - Bouillot, C
AU  - Bouillot C
FAU - Valenza, C
AU  - Valenza C
FAU - Prochiantz, A
AU  - Prochiantz A
FAU - Allinquant, B
AU  - Allinquant B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for
      Neuroscience
JID - 8102140
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Antibodies)
RN  - 0 (Peptides)
RN  - 0 (Sphingolipids)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Axons/metabolism
MH  - Brain/metabolism
MH  - COS Cells
MH  - Cell Compartmentation/*physiology
MH  - Cell Membrane/metabolism
MH  - Cholesterol/metabolism
MH  - Embryo, Mammalian
MH  - GTP Phosphohydrolases/drug effects/metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Immunohistochemistry
MH  - Molecular Sequence Data
MH  - Neurons/metabolism
MH  - Peptides/pharmacology
MH  - Protein Binding/drug effects
MH  - Rats
MH  - Signal Transduction/*physiology
MH  - Sphingolipids/metabolism
PMC - PMC6782156
EDAT- 1999/02/19 00:00
MHDA- 1999/02/19 00:01
CRDT- 1999/02/19 00:00
PHST- 1999/02/19 00:00 [pubmed]
PHST- 1999/02/19 00:01 [medline]
PHST- 1999/02/19 00:00 [entrez]
PST - ppublish
SO  - J Neurosci. 1999 Mar 1;19(5):1717-27.