Kanatsu Y.,Tohoku Pharmaceutical University |
Kanatsu Y.,Core Res. for Evolutional Science and Technology Program of Japan Science and Technology Corporation |
Chen N.H.,Peking Union Medical College |
Mitoma J.,Tohoku Pharmaceutical University |
And 7 more authors.
Journal of Biochemistry | Year: 2012
Gangliosides mediate neuronal differentiation and maturation and are indispensable for the maintenance of brain function and survival. As part of our ongoing efforts to understand signaling pathways related to ganglioside function, we recently demonstrated that neuronal cells react to exogenous gangliosides GT1b and GD1b. Both of these gangliosides are enriched in the synapse-forming area of the brain and induce Ca2+ release from intracellular stores, activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and activation of cdc42 to promote reorganization of cytoskeletal actin and dendritic differentiation. Here, we show that bradykinin B2 receptors transduce these reactions as a mediator for ganglioside glycan signals. The B2 antagonist Hoe140 inhibited ganglioside-induced CaMKII activation, actin reorganization and early development of axon-and dendrite-like processes of primary cultured hippocampal neurons. Furthermore, we confirmed by yeast reporter assay that major b-series gangliosides, GT1b, GD1b and GD3, stimulated B2 bradykinin receptors. We hypothesize that this B2 receptor-mediated ganglioside signal transduction pathway is one mechanism that modulates neuronal differentiation and maturation. The Authors 2012. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved2012 © The Authors 2012. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.