Nakayama Minoru, Matsushita Fumiya, Hama Chihiro
Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan.
Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
J Neurosci. 2014 Oct 15;34(42):13872-7. doi: 10.1523/JNEUROSCI.1585-14.2014.
The synaptic cleft, a crucial space involved in neurotransmission, is filled with extracellular matrix that serves as a scaffold for synaptic differentiation. However, little is known about the proteins present in the matrix and their functions in synaptogenesis, especially in the CNS. Here, we report that Hikaru genki (Hig), a secreted protein with an Ig motif and complement control protein domains, localizes specifically to the synaptic clefts of cholinergic synapses in the Drosophila CNS. The data indicate that this specific localization is achieved by capture of secreted Hig in synaptic clefts, even when it is ectopically expressed in glia. In the absence of Hig, the cytoskeletal scaffold protein DLG accumulated abnormally in cholinergic postsynapses, and the synaptic distribution of acetylcholine receptor (AchR) subunits Dα6 and Dα7 significantly decreased. hig mutant flies consistently exhibited resistance to the AchR agonist spinosad, which causes lethality by specifically activating the Dα6 subunit, suggesting that loss of Hig compromises the cholinergic synaptic activity mediated by Dα6. These results indicate that Hig is a specific component of the synaptic cleft matrix of cholinergic synapses and regulates their postsynaptic organization in the CNS.
突触间隙是神经传递过程中的一个关键空间，充满了细胞外基质，这些基质为突触分化提供了支架。然而，对于基质中存在的蛋白质及其在突触形成中的功能，尤其是在中枢神经系统中的功能，我们了解甚少。在此，我们报告了光神（Hig），一种具有免疫球蛋白基序和补体控制蛋白结构域的分泌蛋白，特异性定位于果蝇中枢神经系统中胆碱能突触的突触间隙。数据表明，即使Hig在神经胶质细胞中异位表达，这种特异性定位也是通过将分泌的Hig捕获到突触间隙中来实现的。在没有Hig的情况下，细胞骨架支架蛋白DLG在胆碱能突触后异常积累，乙酰胆碱受体（AchR）亚基Dα6和Dα7的突触分布显著减少。hig突变体果蝇始终表现出对AchR激动剂多杀菌素的抗性，多杀菌素通过特异性激活Dα6亚基导致致死性，这表明Hig的缺失损害了由Dα6介导的胆碱能突触活性。这些结果表明，Hig是胆碱能突触突触间隙基质的一种特异性成分，并调节中枢神经系统中它们的突触后组织。
