Kohsaka Hiroshi, Takasu Etsuko, Nose Akinao
Department of Physics, Graduate School of Science, Graduate School of Frontier Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Cell Biol. 2007 Dec 17;179(6):1289-300. doi: 10.1083/jcb.200705154. Epub 2007 Dec 10.
Cell adhesion molecules (CAMs) are thought to mediate interactions between innervating axons and their targets. However, such interactions have not been directly observed in vivo. In this paper, we study the function and dynamics of Fasciclin2 (Fas2), a homophilic CAM expressed both pre- and postsynaptically during neuromuscular synapse formation in Drosophila melanogaster. We apply live imaging of functional fluorescent fusion proteins expressed in muscles and find that Fas2 and Discs-Large (Dlg; a scaffolding protein known to bind Fas2) accumulate at the synaptic contact site soon after the arrival of the nerve. Genetic, deletion, and photobleaching analyses suggest that Fas2-mediated trans-synaptic adhesion is important for the postsynaptic accumulation of both Fas2 itself and Dlg. In fas2 mutants, many aspects of synapse formation appear normal; however, we see a reduction in the synaptic accumulation of Scribble (another scaffolding protein) and glutamate receptor subunits GluRIIA and GluRIIB. We propose that Fas2 mediates trans-synaptic adhesion, which contributes to postsynaptic molecular assembly at the onset of synaptogenesis.
细胞黏附分子（CAMs）被认为介导了支配轴突与其靶标之间的相互作用。然而，这种相互作用尚未在体内被直接观察到。在本文中，我们研究了果蝇黑腹果蝇神经肌肉突触形成过程中在突触前和突触后均有表达的同嗜性细胞黏附分子Fasciclin2（Fas2）的功能和动态变化。我们对肌肉中表达的功能性荧光融合蛋白进行实时成像，发现Fas2和盘状大蛋白（Dlg；一种已知与Fas2结合的支架蛋白）在神经到达后不久就聚集在突触接触部位。遗传学、缺失和光漂白分析表明，Fas2介导的跨突触黏附对于Fas2自身和Dlg在突触后的积累很重要。在fas2突变体中，突触形成的许多方面看起来正常；然而，我们发现Scribble（另一种支架蛋白）以及谷氨酸受体亚基GluRIIA和GluRIIB的突触积累减少。我们提出，Fas2介导跨突触黏附，这有助于在突触发生开始时进行突触后分子组装。
