Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion.
Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion.
复制标题
依赖于剪接的反式突触Salm3-lar-RPTP相互作用调节兴奋性突触的发育和运动。
DOI：
10.1016/j.celrep.2015.08.002
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发表时间：
2015-09-08
期刊：
影响因子：
8.8
通讯作者：
Kim E
中科院分区：
文献类型：
--
作者：
Li Y;Zhang P;Choi TY;Park SK;Park H;Lee EJ;Lee D;Roh JD;Mah W;Kim R;Kim Y;Kwon H;Bae YC;Choi SY;Craig AM;Kim E
突触粘附分子调节突触发育和可塑性的各个方面。SALM 3是一种与PSD-95相互作用的突触粘附分子，已知在接触轴突中诱导突触前分化，但对其突触前受体和体内功能知之甚少。在这里，我们确定了SALM 3和LAR家族受体蛋白酪氨酸磷酸酶（LAR-RPTPs）之间的相互作用，需要在LAR-RPTPs中插入小外显子B剪接。此外，SALM 3依赖的突触前分化需要所有三种类型的LAR-RPTP。SALM 3突变（Salm 3 −/−）小鼠在海马CA 1区表现出兴奋性突触数量显著减少，但突触可塑性正常。Salm 3 −/−小鼠在新的和熟悉的环境中都表现出活动减退，但在学习和记忆测试中表现正常。这些结果表明，SALM 3调节兴奋性突触发育和运动行为。SALM 3是一种突触后粘附分子，已知其调节突触发育，但其潜在机制尚不清楚。Li等人发现SALM 3以剪接依赖性方式与突触前LAR家族受体蛋白酪氨酸磷酸酶（LAR-RPTP）相互作用。此外，他们还发现SALM 3突变小鼠表现出兴奋性突触数量减少和活动减退。
Synaptic adhesion molecules regulate diverse aspects of synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3−/−) mice display markedly reduced excitatory synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3−/− mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates excitatory synapse development and locomotion behavior. In Brief SALM3 is a postsynaptic adhesion molecule known to regulate synapse development, but the underlying mechanism remains unclear. Li et al. find that SALM3 interacts with presynaptic LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) in a splicing-dependent manner. In addition, they show that SALM3-mutant mice display reduced excitatory synapse number and hypoactivity.