Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes.
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Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. / Wang, Shiwei; Cesca, Fabrizia; Loers, Gabriele; Schweizer, Michaela; Buck, Friedrich; Benfenati, Fabio; Schachner, Melitta; Kleene, Ralf.
in: J NEUROSCI, Jahrgang 31, Nr. 20, 20, 2011, S. 7275-7290.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes.
AU - Wang, Shiwei
AU - Cesca, Fabrizia
AU - Loers, Gabriele
AU - Schweizer, Michaela
AU - Buck, Friedrich
AU - Benfenati, Fabio
AU - Schachner, Melitta
AU - Kleene, Ralf
PY - 2011
Y1 - 2011
N2 - Oligomannosidic glycans play important roles in nervous system development and function. By performing a phage display screening with oligomannose-specific antibodies, we identified an oligomannose-mimicking peptide that was functionally active in modulating neurite outgrowth and neuron-astrocyte adhesion. Using the oligomannose-mimicking peptide in crosslinking experiments, synapsin I was identified as a novel oligomannose-binding protein in mouse brain. Further analyses not only verified that synapsin I is an oligomannose-binding lectin, but also indicated that it is a glycoprotein carrying oligomannose and Lewis(x). We also found that synapsin I is expressed in glia-enriched cultures and is released from glial cells via exosomes. Incubation of glial-derived exosomes in the presence of high KCl concentrations or subjecting glial cell cultures to either oxygen/glucose deprivation or hydrogen peroxide resulted in release of synapsin I from exosomes. Application of synapsin I promoted neurite outgrowth from hippocampal neurons and increased survival of cortical neurons upon hydrogen peroxide treatment or oxygen/glucose deprivation. Coculture experiments using wild-type hippocampal neurons and wild-type or synapsin-deficient glial cells showed enhanced neurite outgrowth when synapsin was expressed by glial cells. Synapsin-induced neurite outgrowth was dependent on oligomannose on synapsin I and the neural cell adhesion molecule NCAM at the neuronal cell surface. The data indicate that, under conditions of high neuronal activity and/or oxidative stress, synapsin can be released from glial-derived exosomes and promotes neurite outgrowth and neuronal survival by modulating the interactions between glia and neurons.
AB - Oligomannosidic glycans play important roles in nervous system development and function. By performing a phage display screening with oligomannose-specific antibodies, we identified an oligomannose-mimicking peptide that was functionally active in modulating neurite outgrowth and neuron-astrocyte adhesion. Using the oligomannose-mimicking peptide in crosslinking experiments, synapsin I was identified as a novel oligomannose-binding protein in mouse brain. Further analyses not only verified that synapsin I is an oligomannose-binding lectin, but also indicated that it is a glycoprotein carrying oligomannose and Lewis(x). We also found that synapsin I is expressed in glia-enriched cultures and is released from glial cells via exosomes. Incubation of glial-derived exosomes in the presence of high KCl concentrations or subjecting glial cell cultures to either oxygen/glucose deprivation or hydrogen peroxide resulted in release of synapsin I from exosomes. Application of synapsin I promoted neurite outgrowth from hippocampal neurons and increased survival of cortical neurons upon hydrogen peroxide treatment or oxygen/glucose deprivation. Coculture experiments using wild-type hippocampal neurons and wild-type or synapsin-deficient glial cells showed enhanced neurite outgrowth when synapsin was expressed by glial cells. Synapsin-induced neurite outgrowth was dependent on oligomannose on synapsin I and the neural cell adhesion molecule NCAM at the neuronal cell surface. The data indicate that, under conditions of high neuronal activity and/or oxidative stress, synapsin can be released from glial-derived exosomes and promotes neurite outgrowth and neuronal survival by modulating the interactions between glia and neurons.
KW - Animals
KW - Male
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Coculture Techniques
KW - Pregnancy
KW - Protein Binding/physiology
KW - Lectins/metabolism
KW - Cell Communication/genetics/physiology
KW - Cell Survival/genetics/physiology
KW - Exosomes/metabolism/secretion
KW - Glycoproteins/metabolism/secretion
KW - Mannose/metabolism/secretion
KW - Neural Cell Adhesion Molecules/deficiency/genetics
KW - Neurites/metabolism/secretion
KW - Neuroglia/metabolism/secretion
KW - Neurons/metabolism/secretion
KW - Oligosaccharides/metabolism/secretion
KW - Synapsins/metabolism/secretion
KW - Animals
KW - Male
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Coculture Techniques
KW - Pregnancy
KW - Protein Binding/physiology
KW - Lectins/metabolism
KW - Cell Communication/genetics/physiology
KW - Cell Survival/genetics/physiology
KW - Exosomes/metabolism/secretion
KW - Glycoproteins/metabolism/secretion
KW - Mannose/metabolism/secretion
KW - Neural Cell Adhesion Molecules/deficiency/genetics
KW - Neurites/metabolism/secretion
KW - Neuroglia/metabolism/secretion
KW - Neurons/metabolism/secretion
KW - Oligosaccharides/metabolism/secretion
KW - Synapsins/metabolism/secretion
M3 - SCORING: Journal article
VL - 31
SP - 7275
EP - 7290
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 20
M1 - 20
ER -
