INFLUENCE OF ENDOGENOUS GM1 GANGLIOSIDE ON TRKB ACTIVITY, IN CULTUREDNEURONS

We verified the hypothesis that changes in the endogenous GM1 ganglios ide density in the environment of TrkB, receptor of brain-derived neur otrophic factor, can affect receptor activity, and focused on rat cere bellar granule cells expressing both GM1 and TrkB, Changes of the amou nt of GM1 associated to immunoprecipitated TrkB and of receptor tyrosi ne phosphorylation were evaluated after treatment with phorbol-12- myr istate-13-acetate (1 mu M, 7 min), reported to affect the plasma membr ane distribution of endogenous gangliosides in the same cells. After t reatment, the amount of GM1 associated to receptor and TrkB phosphoryl ation decreased by about 40%. The amount of associated GM1 decreased b y about 33% also after concomitant treatment with phorbol ester and br ain-derived neurotrophic factor, but in this case the neurotrophin was unable to enhance receptor tyrosine phosphorylation, These results fo r the first time suggest that changes in the amount of endogenous GM1 in the environment of TrkB can modulate receptor activity, and offer n ew clues for a better understanding of physiological and pathological events of the nervous system. (C) 1998 Federation of European Biochemi cal Societies.