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 (Gg 3 ) Cer, GalNAcα3GalNAcβ3Galα4Galβ4GlcCer (Gb 5 ) 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 language | English |
|---|---|
| Pages (from-to) | 985-995 |
| Number of pages | 11 |
| Journal | Neuroscience |
| Volume | 122 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jan 1 2003 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
Cite this
Extracellular carbohydrate-signal triggering cAMP-dependent protein kinase-dependent neuronal actin-reorganization. / Chen, N.; Furuya, Shigeki; Shinoda, Y.; Yumoto, M.; Ohtake, A.; Sato, K.; Doi, H.; Hashimoto, Y.; Kudo, Y.; Higashi, H.
In: Neuroscience, Vol. 122, No. 4, 01.01.2003, p. 985-995.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Extracellular carbohydrate-signal triggering cAMP-dependent protein kinase-dependent neuronal actin-reorganization
AU - Chen, N.
AU - Furuya, Shigeki
AU - Shinoda, Y.
AU - Yumoto, M.
AU - Ohtake, A.
AU - Sato, K.
AU - Doi, H.
AU - Hashimoto, Y.
AU - Kudo, Y.
AU - Higashi, H.
PY - 2003/1/1
Y1 - 2003/1/1
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 (Gg 3 ) Cer, GalNAcα3GalNAcβ3Galα4Galβ4GlcCer (Gb 5 ) 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 (Gg 3 ) Cer, GalNAcα3GalNAcβ3Galα4Galβ4GlcCer (Gb 5 ) 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.
UR - http://www.scopus.com/inward/record.url?scp=10744219737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744219737&partnerID=8YFLogxK
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 -