Bio Imaging and Cell Dynamics Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
PLoS One. 2013;8(1):e54276. doi: 10.1371/journal.pone.0054276. Epub 2013 Jan 14.
The correct rearrangement of postsynaptic components in dendritic spines is important for driving changes of spine structure and synaptic function. SPIN90 plays an essential role in many cellular processes including actin polymerization, endocytosis, growth cone formation and dendritic spine morphogenesis. Here, we demonstrate that SPIN90, which is a binding partner of PSD95 and Shank in spines, is targeted to synapses and leads to enhanced synaptic activity in neurons. We show, using in vitro and in vivo kinase assays, that SPIN90 is tyrosine phosphorylated by Src kinase. SPIN90 that was tyrosine-phosphorylated by Src was targeted to dendritic spines in cultured hippocampal neurons. Moreover, a SPIN90 phospho-deficient mutant was unable to accumulate at dendritic spines whereas SPIN90 WT and a phospho-mimicking mutant were localized at spines and bound PSD95 and Shank with increased efficiency. Consistent with these findings, hippocampal neurons that overexpressed SPIN90 WT or a phospho-mimicking mutant had enlarged spine heads, leading to enhanced postsynaptic function in terms of both amplitude and frequency. Together, our findings show that SPIN90 modulates synaptic activity in neurons as a result of its phosphorylation.
正确排列树突棘内的突触后成分对于驱动棘突结构和突触功能的变化很重要。SPIN90 在许多细胞过程中发挥着重要作用，包括肌动蛋白聚合、内吞作用、生长锥形成和树突棘形态发生。在这里，我们证明 SPIN90 是 PSD95 和 Shank 在棘突中的结合伴侣，它被靶向到突触，并导致神经元中的突触活性增强。我们使用体外和体内激酶测定法表明，Src 激酶使 SPIN90 酪氨酸磷酸化。Src 磷酸化的 SPIN90 被靶向到培养的海马神经元中的树突棘。此外，SPIN90 磷酸缺陷突变体不能聚集在树突棘上，而 SPIN90 WT 和磷酸模拟突变体则定位于棘突上，并以更高的效率与 PSD95 和 Shank 结合。与这些发现一致的是，过度表达 SPIN90 WT 或磷酸模拟突变体的海马神经元的棘突头部增大，导致突触后功能在幅度和频率方面都增强。总之，我们的研究结果表明，SPIN90 通过其磷酸化调节神经元中的突触活性。
