Ganglioside inhibition of glutamate-mediated protein kinase C translocation in primary cultures of cerebellar neurons

Journal Article · Tue Dec 01 04:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.23.8707· OSTI ID:6408832

Vaccarino, F; Guidotti, A; Costa, E

In primary cultures of cerebellar granule cells, protein kinase C (PKC) translocation and activation can be triggered by the stimulation of excitatory amino acid neurotransmitter receptors. Glutamate evokes a dose-related translocation of 4-..beta..-(/sup 3/H)phorbol 12,13-dibutyrate /(/sup 3/H)-P(BtO)/sub 2// binding sites from the cytosol to the neuronal membrane and stimulates the incorporation of /sup 32/P into a number of membrane proteins, particularly protein bands in the range of 80, 50, and 40 kDa. The glutamate-evoked PKC translocation is Mg/sup 2 +/ sensitive, is prevented by 2-amino-5-phosphonovalerate and phencyclidine, is not inhibited by nitrendipine (a voltage-dependent Ca/sup 2 +/-channel-blocker) but is abolished by the removal of Ca/sup 2 +/ from the incubation medium, suggesting that glutamate-mediated Ca/sup 2 +/ influx is operative in the redistribution of PKC. Exposure of granule cells to the gangliosides trisialosylgangliotetraglycosylceramide (GT1b) of monosialosylgangliotetraglycosylceramide (GM1) inhibits the translocation and activation of PKC evoked by glutamate. These glycosphingolipids fail to interfere with glutamate binding to its high-affinity recognition site of with the (/sup 3/H)P(BtO)/sub 2/ binding, nor do they affect the Ca/sup 2 +/ influx. These gangliosides may prevent PKC translocation by interfering with the PKC binding to the neuronal membrane phosphatidylserine.

• Research Organization: Georgetown Univ. Medical School, Washington, DC (USA)
• OSTI ID: 6408832
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:23; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BODY
BRAIN
CARBOHYDRATES
CARBOXYLIC ACIDS
CARCINOGENS
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CEREBRUM
CHEMICAL REACTIONS
CHEMISTRY
CROSS-LINKING
CYTOPLASM
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
DOSE-RESPONSE RELATIONSHIPS
ENZYMES
ESTERS
GANGLIOSIDES
GLUTAMIC ACID
GLYCOLIPIDS
INHIBITION
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIPIDS
MEMBRANE PROTEINS
MEMBRANES
NERVE CELLS
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHORBOL ESTERS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
POLYMERIZATION
PROTEINS
RADIOISOTOPES
RECEPTORS
SACCHARIDES
SOMATIC CELLS
SUBCELLULAR DISTRIBUTION
TRANSFERASES
TRITIUM COMPOUNDS