TY - JOUR
T1 - Extracellular carbohydrate-signal triggering cAMP-dependent protein kinase-dependent neuronal actin-reorganization
AU - Chen, N.
AU - Furuya, S.
AU - Shinoda, Y.
AU - Yumoto, M.
AU - Ohtake, A.
AU - Sato, K.
AU - Doi, H.
AU - Hashimoto, Y.
AU - Kudo, Y.
AU - Higashi, H.
N1 - Funding Information:
This work was partially supported by a Grant-in-Aid for Scientific Research on Priority Areas (No. 10178105) from the Ministry of Education, Science, Sports and Culture of Japan. We are grateful to Dr. M. Negishi at Kyoto University for providing plasmids, to Dr. Y. Hirabayashi of RIKEN Brain Science Institute for materials and encouragement, and Dr. S. Ono of Emory University for valuable discussion. We thank Dr. Y. Fukazawa, T. Saitoh, and M. Sekiguchi for their technical advice, Y. Akasako for her valuable assistance and Dr. Yoshitaka Nagai for encouragement at Mitsubishi Kagaku Institute of Life Sciences.
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuroscience.2003.08.042
DO - 10.1016/j.neuroscience.2003.08.042
M3 - Article
C2 - 14643765
AN - SCOPUS:10744219737
VL - 122
SP - 985
EP - 995
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 4
ER -