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Essential Role of Latrophilin-1 Adhesion GPCR Nanoclusters in Inhibitory Synapses
Journal of Neuroscience ( IF 4.4 ) Pub Date : 2024-06-05 , DOI: 10.1523/jneurosci.1978-23.2024
Daniel Matúš , Jaybree M. Lopez , Richard C. Sando , Thomas C. Südhof

Latrophilin-1 (Lphn1, aka CIRL1 and CL1; gene symbol Adgrl1) is an adhesion GPCR that has been implicated in excitatory synaptic transmission as a candidate receptor for α-latrotoxin. Here we analyzed conditional knock-in/knock-out mice for Lphn1 that contain an extracellular myc epitope tag. Mice of both sexes were used in all experiments. Surprisingly, we found that Lphn1 is localized in cultured neurons to synaptic nanoclusters that are present in both excitatory and inhibitory synapses. Conditional deletion of Lphn1 in cultured neurons failed to elicit a detectable impairment in excitatory synapses but produced a decrease in inhibitory synapse numbers and synaptic transmission that was most pronounced for synapses close to the neuronal soma. No changes in axonal or dendritic outgrowth or branching were observed. Our data indicate that Lphn1 is among the few postsynaptic adhesion molecules that are present in both excitatory and inhibitory synapses and that Lphn1 by itself is not essential for excitatory synaptic transmission but is required for some inhibitory synaptic connections.



中文翻译:


Latrophilin-1 粘附 GPCR 纳米簇在抑制性突触中的重要作用



Latrophilin-1(Lphn1,又名 CIRL1 和 CL1;基因符号 Adgrl1)是一种粘附 GPCR,作为 α-latrotoxin 的候选受体参与兴奋性突触传递。在这里,我们分析了含有细胞外 myc 表位标签的 Lphn1 的条件敲入/敲除小鼠。所有实验均使用两种性别的小鼠。令人惊讶的是,我们发现 Lphn1 定位于培养的神经元中的突触纳米簇,这些纳米簇存在于兴奋性和抑制性突触中。在培养的神经元中条件性删除 Lphn1 未能引起可检测到的兴奋性突触损伤,但会导致抑制性突触数量和突触传递减少,这对于靠近神经元胞体的突触最为明显。没有观察到轴突或树突生长或分支的变化。我们的数据表明,Lphn1 是少数同时存在于兴奋性和抑制性突触中的突触后粘附分子之一,并且 Lphn1 本身对于兴奋性突触传递不是必需的,但对于某些抑制性突触连接是必需的。

更新日期:2024-06-06
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