Extracellular carbohydrate-signal triggering cAMP-dependent protein kinase-dependent neuronal actin-reorganization

N. Chen, S. Furuya, Y. Shinoda, M. Yumoto, A. Ohtake, K. Sato, H. Doi, Y. Hashimoto, Y. Kudo, H. Higashi

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Cell surface glycoconjugates are thought to mediate cell-cell recognition and to play roles in neuronal development and functions. We demonstrated here that exposure of neuronal cells to nanomolar levels of glyco-chains with an N-acetylgalactosamine (GalNAc) residue at the non-reducing termini (GalNAc-S) such as GalNAcβ4(Neu5Acα3)Galβ4GlcCer (GM2) ganglioside, its oligosaccharide portion, GalNAcβ4Galβ4GlcCer (Gg3) Cer, GalNAcα3GalNAcβ3Galα4Galβ4GlcCer (Gb5) Cer (Forssman hapten) and α1-4 linked oligomers of GalNAc, induced a rapid and transient activation of cAMP-dependent protein kinase (PKA) in subplasmalemma. The treatment was accompanied by peripheral actin polymerization and filopodia formation in NG108-15 cells and primary cultured hippocampal neurons, but not in glial cells. A cAMP-dependent protein kinase (PKA) selective inhibitor and an adenylate cyclase inhibitor blocked both PKA activation and the subsequent filopodia formation. A small GTPase cdc42 was a potential downstream target of GalNAc-S-activated PKA. These results suggest that extracellular GalNAc-S serve as potential regulators of the filopodia formation in neuronal cells by triggering the activation of PKA followed by cdc42 up-regulation via a cell surface receptor-like component. Filopodia formation induced by GalNAc-S may have a physiological relevance because long-term exposure to GalNAc-S enhanced F-actin-rich dendrite generation of primary cultured hippocampal neurons, and PKA-dependent dendritic outgrowth and branch formation of primary cultured cerebellar Purkinje neurons, in which actin isoforms were localized to motile structures in dendrites. These findings provide evidence for a novel GalNAc/PKA-signaling cascade in regulating some neuronal maturation.

Original languageEnglish
Pages (from-to)985-995
Number of pages11
JournalNeuroscience
Volume122
Issue number4
DOIs
Publication statusPublished - Jan 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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