Bozdagi Ozlem, Valcin Martin, Poskanzer Kira, Tanaka Hidekazu, Benson Deanna L
Fishberg Department of Neuroscience, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Mol Cell Neurosci. 2004 Dec;27(4):509-21. doi: 10.1016/j.mcn.2004.08.008.
Classic cadherins are synaptic adhesion proteins that have been implicated in synapse formation and targeting. Brief inactivation of classic cadherin function in young neurons appears to abrogate synapse formation when examined acutely. It remains unknown if such abrogation is unique to young neurons, whether it occurs by stalling neuronal maturation or by directly interfering with the process of synapse assembly, or whether synapse targeting is altered. Here we asked if sustained pan-cadherin blockade would prevent or alter the progression of axonal and dendritic outgrowth, synaptogenesis, or the stereotypic distribution of excitatory and inhibitory synapses on cultured hippocampal neurons. While pre- and postsynaptic cadherins are required for synapse assembly in young neurons, we find that in neurons older than 10 days, classic cadherins are entirely dispensable for joining and aligning presynaptic vesicle clusters with molecular markers of the postsynaptic density. Furthermore, we find that the proportion and relative distributions of excitatory and inhibitory terminals on single neurons are not altered. However, synapses that form on neurons in which cadherin function is blocked are smaller; they exhibit decreased synaptic vesicle recycling and a decreased frequency of spontaneous EPSCs. Moreover, they fail to acquire resistance to F-actin depolymerization, a hallmark of mature, stable contacts. These data provide new evidence that cadherins are required to promote synapse stabilization and structural and functional maturation, but dispensable for the correct subcellular distribution of excitatory and inhibitory synapses.
经典钙黏蛋白是突触黏附蛋白,与突触形成和靶向有关。急性检查时,年轻神经元中经典钙黏蛋白功能的短暂失活似乎会消除突触形成。目前尚不清楚这种消除是否是年轻神经元所特有的,它是通过阻止神经元成熟还是直接干扰突触组装过程而发生的,或者突触靶向是否会改变。在这里,我们询问持续的泛钙黏蛋白阻断是否会阻止或改变培养的海马神经元轴突和树突生长、突触形成或兴奋性和抑制性突触的刻板分布的进程。虽然年轻神经元的突触组装需要突触前和突触后的钙黏蛋白,但我们发现,在10天以上的神经元中,经典钙黏蛋白对于将突触前囊泡簇与突触后密度的分子标记物连接和对齐是完全不必要的。此外,我们发现单个神经元上兴奋性和抑制性终末的比例和相对分布没有改变。然而,在钙黏蛋白功能被阻断的神经元上形成的突触较小;它们表现出突触囊泡循环减少和自发兴奋性突触后电流频率降低。此外,它们无法获得对F-肌动蛋白解聚的抗性,这是成熟、稳定接触的一个标志。这些数据提供了新的证据,表明钙黏蛋白是促进突触稳定以及结构和功能成熟所必需的,但对于兴奋性和抑制性突触的正确亚细胞分布是不必要的。