Wnt-5a/JNK Signaling Promotes the Clustering of PSD-95 in Hippocampal Neurons
Wnt-5a/JNK Signaling Promotes the Clustering of PSD-95 in Hippocampal Neurons
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DOI：
10.1074/jbc.m808986200
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发表时间：
2009-06-05
影响因子：
4.8
通讯作者：
Inestrosa, Nibaldo C.
中科院分区：
文献类型：
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作者：
Farias, Ginny G.;Alfaro, Ivan E.;Inestrosa, Nibaldo C.
在突触形成过程中，突触前和突触后细胞的特定区域相互联系，形成一个单一的功能传递单元。在这个过程中，突触发生因子是调节突触前和突触后分化所必需的。在哺乳动物中，不同的Wnt配体通过规范和非规范的Wnt通路起作用，它们在成熟中枢神经系统中协调突触结构和功能的精确功能在很大程度上仍然未知。本研究研究了不同Wnt配体对突触后组织的影响。我们发现Wnt-5a诱导PSD-95聚类的短期变化，而不影响其总水平。Wnt-5a促进分散的树突细胞质池中PSD-95的募集，在树突棘中形成新的PSD-95簇。此外，Wnt-5a作为非规范配体通过jnk依赖的信号通路调节PSD-95的分布，在成熟海马神经元中使用TAT-TI-JIP肽证明了这一点。最后，利用成年大鼠海马切片，我们发现Wnt-5a通过突触后机制调节谷氨酸能突触传递。我们的研究表明，Wnt-5a/JNK通路调节哺乳动物突触的突触后区域，指导生理相关支架蛋白PSD-95的聚集和分布。
During the formation of synapses, specific regions of pre- and postsynaptic cells associate to form a single functional transmission unit. In this process, synaptogenic factors are necessary to modulate pre- and postsynaptic differentiation. In mammals, different Wnt ligands operate through canonical and non-canonical Wnt pathways, and their precise functions to coordinate synapse structure and function in the mature central nervous system are still largely unknown. Here, we studied the effect of different Wnt ligands on postsynaptic organization. We found that Wnt-5a induces short term changes in the clustering of PSD-95, without affecting its total levels. Wnt-5a promotes the recruitment of PSD-95 from a diffuse dendritic cytoplasmic pool to form new PSD-95 clusters in dendritic spines. Moreover, Wnt-5a acting as a non-canonical ligand regulates PSD-95 distribution through a JNK-dependent signaling pathway, as demonstrated by using the TAT-TI-JIP peptide in mature hippocampal neurons. Finally, using adult rat hippocampal slices, we found that Wnt-5a modulates glutamatergic synaptic transmission through a postsynaptic mechanism. Our studies indicate that the Wnt-5a/JNK pathway modulates the postsynaptic region of mammalian synapse directing the clustering and distribution of the physiologically relevant scaffold protein, PSD-95.