瑞典哥德堡大学Fredrik H. Sterky等研究人员合作发现，liprin-α蛋白是人类突触前组装的核心调控因子。相关论文于2024年3月12日在线发表在《自然—神经科学》杂志上。

在无脊椎动物开创性工作的指导下，研究人员假设在哺乳动物的突触中，liprin-α蛋白直接将跨突触的初始接触与下游步骤联系起来。研究人员发现，在缺乏所有四种liprin-α亚型的人类神经元中，新生突触接触得以形成，但活性区成分的招募和突触小泡的积聚受阻，从而导致“空”突触和突触传递的丧失。

需要通过CASK与LAR-RPTP家族的突触前细胞粘附分子或神经毒素相互作用，才能将liprin-α定位于新生突触位点。随后，liprin-α通过与ELKS蛋白的直接相互作用来招募突触前成分。因此，人类突触前末端的组装受一系列分层事件的支配，其中突触前细胞粘附分子招募liprin-α蛋白是关键的第一步。

据悉，哺乳动物突触的形成需要突触前释放位点与突触后受体的精确配准，但新生细胞-细胞接触如何转化为突触前特化的组装仍不清楚。

附：英文原文

Title: Liprin-α proteins are master regulators of human presynapse assembly

Author: Marc de la Cruz, Berta, Campos, Joaqun, Molinaro, Angela, Xie, Xingqiao, Jin, Gaowei, Wei, Zhiyi, Acuna, Claudio, Sterky, Fredrik H.

Issue&Volume: 2024-03-12

Abstract: The formation of mammalian synapses entails the precise alignment of presynaptic release sites with postsynaptic receptors but how nascent cell–cell contacts translate into assembly of presynaptic specializations remains unclear. Guided by pioneering work in invertebrates, we hypothesized that in mammalian synapses, liprin-α proteins directly link trans-synaptic initial contacts to downstream steps. Here we show that, in human neurons lacking all four liprin-α isoforms, nascent synaptic contacts are formed but recruitment of active zone components and accumulation of synaptic vesicles is blocked, resulting in ‘empty’ boutons and loss of synaptic transmission. Interactions with presynaptic cell adhesion molecules of either the LAR-RPTP family or neurexins via CASK are required to localize liprin-α to nascent synaptic sites. Liprin-α subsequently recruits presynaptic components via a direct interaction with ELKS proteins. Thus, assembly of human presynaptic terminals is governed by a hierarchical sequence of events in which the recruitment of liprin-α proteins by presynaptic cell adhesion molecules is a critical initial step.

DOI: 10.1038/s41593-024-01592-9

Source: https://www.nature.com/articles/s41593-024-01592-9