Postsynaptic adhesion GPCR latrophilin-2 mediates target recognition in entorhinal-hippocampal synapse assembly
Postsynaptic adhesion GPCR latrophilin-2 mediates target recognition in entorhinal-hippocampal synapse assembly
复制标题
DOI：
10.1083/jcb.201703042
复制
发表时间：
2017-11-01
影响因子：
7.8
通讯作者：
Sudhof, Thomas C.
中科院分区：
文献类型：
--
作者：
Anderson, Garret R.;Maxeiner, Stephan;Sudhof, Thomas C.
突触组装可能需要传入的突触前传入神经对突触后目标的识别。使用新产生的条件性敲入和敲除小鼠，我们在这项研究中表明，latrophilin-2（Lphn 2），细胞粘附G蛋白偶联受体和推定的α-latrotoxin受体，控制CA 1区海马神经元突触的特定子集的数量，这表明Lphn 2作为一个突触的目标识别分子。在培养的海马神经元中，Lphn 2通过突触后而不是突触前机制来维持突触数量，这是令人惊讶的，因为它被假定为α-latrotoxin受体。在体内的CA 1区神经元中，Lphn 2特异性地靶向于腔隙分子层中的树突棘，其与突触前内嗅皮层传入形成突触。在这项研究中，突触后Lphn 2的删除选择性地减少脊柱的数量和受损的突触输入从内嗅，但不谢弗侧支传入。行为上，Lphn 2从CA 1区的损失增加空间记忆保持，但减少学习顺序空间记忆任务。因此，Lphn 2似乎控制内嗅皮层/CA 1区电路作为一个域特异性突触后靶识别分子的突触数量。
Synapse assembly likely requires postsynaptic target recognition by incoming presynaptic afferents. Using newly generated conditional knock-in and knockout mice, we show in this study that latrophilin-2 (Lphn2), a cell-adhesion G protein-coupled receptor and presumptive a-latrotoxin receptor, controls the numbers of a specific subset of synapses in CA1-region hippocampal neurons, suggesting that Lphn2 acts as a synaptic target-recognition molecule. In cultured hippocampal neurons, Lphn2 maintained synapse numbers via a postsynaptic instead of a presynaptic mechanism, which was surprising given its presumptive role as an a-latrotoxin receptor. In CA1-region neurons in vivo, Lphn2 was specifically targeted to dendritic spines in the stratum lacunosum-moleculare, which form synapses with presynaptic entorhinal cortex afferents. In this study, postsynaptic deletion of Lphn2 selectively decreased spine numbers and impaired synaptic inputs from entorhinal but not Schaffer-collateral afferents. Behaviorally, loss of Lphn2 from the CA1 region increased spatial memory retention but decreased learning of sequential spatial memory tasks. Thus, Lphn2 appears to control synapse numbers in the entorhinal cortex/CA1 region circuit by acting as a domain-specific postsynaptic target-recognition molecule.