Ethell I M, Irie F, Kalo M S, Couchman J R, Pasquale E B, Yamaguchi Y
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neuron. 2001 Sep 27;31(6):1001-13. doi: 10.1016/s0896-6273(01)00440-8.
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.
我们先前报道，细胞表面蛋白聚糖syndecan-2可诱导海马神经元树突棘形成。我们在此证明，EphB2受体酪氨酸激酶使syndecan-2磷酸化，且该磷酸化事件对syndecan-2聚集和树突棘形成至关重要。在小鼠大脑中，syndecan-2发生酪氨酸磷酸化并与EphB2形成复合物。对内源性EphB受体活性的显性负抑制可阻断培养的海马神经元中内源性syndecan-2的聚集和正常树突棘形成。这是Eph受体在树突棘形态发生中发挥生理作用的首个证据。我们的观察结果表明，树突棘形态发生是由Eph受体激活引发的，Eph受体激活会导致假定树突棘中诸如syndecan-2等靶分子的酪氨酸磷酸化。
