Regulation of synaptic plasticity by receptor-like protein tyrosine phosphatase

Ptprz的胞外区被基质金属蛋白酶-9或纤溶酶解离，产生其膜系留片段。据报道，当突触重塑发生时，这两种蛋白水解酶都被激活。我们发现Ptprz片段聚集在突触后密度的PSD部分，表明该受体实际上在中央突触处被切割。我们鉴定了Git1和Magi1中的去磷酸化位点。这些底物蛋白中目标磷酸酪氨酸残基周围的初级序列的比对显示出相当大的相似性，这表明Ptprz对底物的识别具有一致的基序。我们发现，由此推导出的底物基序存在于一些蛋白质中，包括巴西林的第118位。最后，我们验证了Ptprz在培养细胞中有效地在这个位置去磷酸化帕西林。

The extracellular region of Ptprz is shedded by MMP-9 or plasmin, producing its membrane-tethered fragment. Both proteases are reportedly activated when synaptic remodeling is occurring. We revealed that Ptprz fragments are accumulated in the post synaptic density PSD fraction, indicating that this receptor is actually cleaved at central synapses. We identified the dephosphorylation sites in Git1 and Magi1. Alignment of the primary sequences surrounding the target phospho-tyrosine residue in these substrate proteins showed a considerable similarity, suggesting a consensus motif for substrate recognition by Ptprz. We found that the substrate motif thus deduced is present in some proteins, including at Tyr118 of paxillin. Finally, we verified that Ptprz efficiently dephosphorylates paxillin at this site in cultured cells.