Discovery of ganglioside GM1 for normal function of Trk neurotrophin receptor in neuronal cells.

What is it about?

High affinity nerve growth factor (NGF) receptor, Trk-tyrosine kinase, is essential for neuronal differentiation and survival in the nervous system. Heretofore, no previous findings of endogenous regulator of Trk-tyrosine kinase before our publication in Proc Natl Acad Sci USA 1995 Mutoh T et al. had been available. In this study, GM1 ganglioside, one of the cardial resident of membrane rafts binds to Trk-neurotrophin receptor in a way of SDS-resistant and regulates it positively. Such strong bindings were not observed on EGF receptor nor low affinity NGF receptor. This study illustrated for the first time that receptor-type tyrosine kinases can bind to gangliosides such as GM1 for Trk and GM3 for EGF receptor-tyrosine kinase and by their binding tyrosine kinase activities get strongly modulated.

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Photo by Jonatan Lewczuk on Unsplash

Photo by Jonatan Lewczuk on Unsplash

Why is it important?

This study illustrated the importance of protein-lipids interaction in the signal transduction pathway. As demonstrated in JBC 1998, if intracellular GM1 is depleted, Trk-neurotrophin receptor is no more responsive again its ligand, NGF. Moreover, among exogenous addition of various gangliosides in the culture medium, only GM1 addition into culture medium rescued the responsiveness of Trk-tyrosine kinase to its ligand, NGF in gangliosides depleted cells. This study illustrated for the first time the endogenous phisiological factor against Trk neurotrophin receptor for its normal function. This study is the first indication that the protein residing in the membrane rafts needs their lipids factors for the normal function of the protein.

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