Yoshida Tomoyuki, Mishina Masayoshi
Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Mol Cell Neurosci. 2008 Oct;39(2):218-28. doi: 10.1016/j.mcn.2008.06.013. Epub 2008 Jul 1.
IL1-receptor accessory protein-like 1 (IL1RAPL1), a member of interleukin-1/toll receptor (TIR) family, is responsible for a nonsyndromic form of mental retardation (MR). The zebrafish orthologue of mammalian IL1RAPL1, designated as Il1rapl1b, was expressed widely in the brain and in the olfactory placode. We employed an olfactory sensory neuron-specific gene manipulation system in combination with in vivo imaging of transparent zebrafish embryos to examine the functional role of Il1rapl1b in synaptic vesicle accumulation and subsequent morphological remodeling of axon terminals, the characteristic features of presynaptic differentiation of zebrafish olfactory sensory neurons during synapse formation. Antisense morpholino oligonucleotide against il1rapl1b suppressed both the synaptic vesicle accumulation and axon terminal remodeling. Consistently, the overexpression of Il1rapl1b stimulated synaptic vesicle accumulation. Swapping the carboxyl-terminal domain of Il1rapl1b with that of mouse IL-1 receptor accessory protein abolished the stimulatory effect. On the other hand, a substitution mutation in the TIR domain suppressed the morphological remodeling of axon terminals. Thus, the regulation of synaptic vesicle accumulation and subsequent morphological remodeling by Il1rapl1b appeared to be mediated by distinct domains. These results suggest that Il1rapl1b plays an important role in presynaptic differentiation during synapse formation.
白细胞介素-1受体辅助蛋白样1（IL1RAPL1）是白细胞介素-1/ Toll样受体（TIR）家族的成员，与一种非综合征型智力障碍（MR）相关。哺乳动物IL1RAPL1在斑马鱼中的同源基因，命名为Il1rapl1b，在脑和嗅基板中广泛表达。我们利用嗅觉感觉神经元特异性基因操纵系统，结合透明斑马鱼胚胎的体内成像技术，来研究Il1rapl1b在突触小泡聚集以及轴突终末随后的形态重塑中的功能作用，这些都是斑马鱼嗅觉感觉神经元在突触形成过程中突触前分化的特征。针对il1rapl1b的反义吗啉代寡核苷酸抑制了突触小泡聚集和轴突终末重塑。同样，Il1rapl1b的过表达刺激了突触小泡聚集。将Il1rapl1b的羧基末端结构域与小鼠白细胞介素-1受体辅助蛋白的结构域进行交换，消除了这种刺激作用。另一方面，TIR结构域中的一个替代突变抑制了轴突终末的形态重塑。因此，Ilrapl1b对突触小泡聚集和随后形态重塑的调节似乎是由不同的结构域介导的。这些结果表明，Il1rapl1b在突触形成过程中的突触前分化中起重要作用。
