Alternative splicing regulates trans‐synaptic adhesions and synapse development, but supporting in vivo evidence is limited. PTP δ, a receptor tyrosine phosphatase adhering to multiple synaptic adhesion molecules, is associated with various neuropsychiatric disorders; however, its in vivo functions remain unclear. Here, we show that PTP δ is mainly present at excitatory presynaptic sites by endogenous PTP δ tagging. Global PTP δ deletion in mice leads to input‐specific decreases in excitatory synapse development and strength. This involves tyrosine dephosphorylation and synaptic loss of IL 1RAPL 1, a postsynaptic partner of PTP δ requiring the PTP δ‐meA splice insert for binding. Importantly, PTP δ‐mutant mice lacking the PTP δ‐meA insert, and thus lacking the PTP δ interaction with IL 1RAPL 1 but not other postsynaptic partners, recapitulate biochemical and synaptic phenotypes of global PTP δ‐mutant mice. Behaviorally, both global and meA‐specific PTP δ‐mutant mice display abnormal sleep behavior and non‐REM rhythms. Therefore, alternative splicing in PTP δ regulates excitatory synapse development and sleep by modulating a specific trans‐synaptic adhesion.

中文翻译：

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剪接依赖性跨突触的PTPδ-IL1RAPL1相互作用调节突触的形成和非REM睡眠。

选择性剪接可调节跨突触的粘附和突触的发育，但在体内支持的证据有限。PTPδ是一种粘附在多个突触粘附分子上的受体酪氨酸磷酸酶，与多种神经精神疾病有关。然而，它的体内功能尚不清楚。在这里，我们通过内源性PTPδ标记显示PTPδ主要存在于兴奋性突触前位点。小鼠中总体PTPδ缺失导致兴奋性突触发育和强度的输入特异性下降。这涉及酪氨酸去磷酸化和IL 1RAPL 1的突触损失，IL 1RAPL 1是PTPδ的突触后伴侣，需要PTPδ-meA剪接插入物才能结合。重要的是，缺少PTPδ-meA插入片段的PTPδ突变小鼠，因此缺乏与IL 1RAPL 1的PTPδ相互作用，但没有其他突触后伴侣，可以概括全球PTPδ突变小鼠的生化和突触表型。从行为上讲，全局和meA特异性PTPδ突变小鼠均表现出异常的睡眠行为和非REM节律。因此，