EphB/syndecan-2 signaling in dendritic spine morphogenesis.
We previously reported that the cell surface proteoglycan syndecan-2 can induce dendritic spine formation in hippocampal neurons. We demonstrate here that the EphB2 receptor tyrosine kinase phosphorylates syndecan-2 and that this phosphorylation event is crucial for syndecan-2 clustering and spine formation. Syndecan-2 is tyrosine phosphorylated and forms a complex with EphB2 in mouse brain. Dominant-negative inhibition of endogenous EphB receptor activities blocks clustering of endogenous syndecan-2 and normal spine formation in cultured hippocampal neurons. This is the first evidence that Eph receptors play a physiological role in dendritic spine morphogenesis. Our observations suggest that spine morphogenesis is triggered by the activation of Eph receptors, which causes tyrosine phosphorylation of target molecules, such as syndecan-2, in presumptive spines.
Ethell
I M
IM
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Irie
F
F
Kalo
M S
MS
Couchman
J R
JR
Pasquale
E B
EB
Yamaguchi
Y
Y
D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D036183:Receptor, EphB2; D015398:Signal Transduction / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053669:Syndecan-2; D014162:Transfection
D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; C508246:Sdc2 protein, mouse; C508247:Sdc2 protein, rat; D053669:Syndecan-2; D019000:Phosphotyrosine; D020794:Receptor Protein-Tyrosine Kinases; D036183:Receptor, EphB2