title: Gangliosides stimulate bradykinin B2 receptors to promote calmodulin kinase II-mediated neuronal differentiation.
abstract: 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 Ca(2+) release from intracellular stores, activation of Ca(2+)/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.
authors.affiliation: Division of Glyco-Signal Research, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kanatsu
authors.forename: Nai Hong
authors.initials: NH
authors.lastname: Chen
authors.forename: Junya
authors.initials: J
authors.lastname: Mitoma
authors.forename: Tetsuto
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Higashi
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004622:Embryo, Mammalian; D005732:Gangliosides / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005732:Gangliosides; D043782:Receptor, Bradykinin B2; C065679:icatibant; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D001920:Bradykinin