Ganglioside/calmodulin kinase II signal inducing cdc42-mediated neuronal actin reorganization

N. Chen, S. Furuya, H. Doi, Y. Hashimoto, Y. Kudo, H. Higashi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Cell surface glycoconjugates are thought to mediate cell-cell recognition and play roles in neuronal development and functions. We demonstrated here that exposure of neuronal cells to nanomolar levels of gangliosides Neu5Acα8Neu5Acα3Galβ4GlcCer, Galβ3GalNAcβ4(Neu5Acα8Neu5Acα3)Galβ4GlcCer (GD1b), Neu5Acα3Galβ3GalNAcβ4(Neu5Acα8Neu5Acα3) Galβ4GlcCer (GT1b) or its oligosaccharide portion induced a rapid and transient activation of Ca2+/calmodulin-dependent protein kinase II (CaM-KII) in the subplasmalemma. Galβ3GalNAcβ4(Neu5Acα3)Galβ4GlcCer (GM1), GalNAcβ4(Neu5Acα3)Galβ4GlcCer, Neu5Acα3Galβ4GlcCer, Neu5Acα3Galβ3GalNAcβ4(Neu5Acα3)Galβ4GlcCer (GD1a), and Neu5Acα8Neu5Acα3Galβ3GalNAcβ4 (Neu5Acα8Neu5Acα3)-Galβ4GlcCer were ineffective. GT1b and GD1b stimulated transient elevation of bulk cytosolic Ca2+ levels while GM1 slightly elevated the levels and GD1a did not. Thus, the cytosolic Ca2+ elevation by the gangliosides may trigger the CaM-KII activation. The treatment was accompanied by peripheral actin polymerization and filopodia formation in NG108-15 cells and primary hippocampal neurons, but not in glial cells. CaM-KII inhibitors blocked both CaM-KII activation and the subsequent filopodia formation. A small G-protein cdc42 was a potential downstream target of CaM-KII activated by the gangliosides. These results suggest that oligosaccharides of the gangliosides serve as potential regulators of the filopodia formation in neuronal cells by triggering the activation of CaM-KII followed by cdc42 up-regulation via a cell surface receptor-like component. The filopodia formation induced by the gangliosides may have a physiological relevance because long-term exposure of hippocampal neurons to GT1b oligosaccharide induced advanced dendritogenesis. Furthermore, exposure of cerebellar neurons to GT1b oligosaccharide facilitated CaM-KII-dependent dendritic outgrowth and branch formation of cerebellar Purkinje neurons, in which actin isoforms were localized to motile structures in dendrites. Thus, the ganglioside/CaM-KII signal plays a role in modulating dendritic morphogenesis by inducing cdc42-mediated actin reorganization.

Original languageEnglish
Pages (from-to)163-176
Number of pages14
JournalNeuroscience
Volume120
Issue number1
DOIs
Publication statusPublished - Aug 4 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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