Sasakura Hiroyuki, Inada Hitoshi, Kuhara Atsushi, Fusaoka Eri, Takemoto Daisuke, Takeuchi Kosei, Mori Ikue
Department of Molecular Biology, Graduate School of Science, Nagoya University, Nagoya, Japan.
EMBO J. 2005 Apr 6;24(7):1477-88. doi: 10.1038/sj.emboj.7600621. Epub 2005 Mar 17.
The L1 family of cell adhesion molecules is predominantly expressed in the nervous system. Mutations in human L1 cause neuronal diseases such as HSAS, MASA, and SPG1. Here we show that sax-7 gene encodes an L1 homologue in Caenorhabditis elegans. In sax-7 mutants, the organization of ganglia and positioning of neurons are abnormal in the adult stage, but these abnormalities are not observed in early larval stage. Misplacement of neurons in sax-7 mutants is triggered by mechanical force linked to body movement. Short and long forms of SAX-7 exhibited strong and weak homophilic adhesion activities in in vitro aggregation assay, respectively, which correlated with their different activities in vivo. SAX-7 was localized on plasma membranes of neurons in vivo. Expression of SAX-7 only in a single neuron in sax-7 mutants cell-autonomously restored its normal neuronal position. Expression of SAX-7 in two different head neurons in sax-7 mutants led to the forced attachment of these neurons. We propose that both homophilic and heterophilic interactions of SAX-7 are essential for maintenance of neuronal positions in organized ganglia.
细胞黏附分子L1家族主要在神经系统中表达。人类L1基因的突变会导致诸如HSAS、MASA和SPG1等神经元疾病。在此我们表明，秀丽隐杆线虫中的sax - 7基因编码一种L1同源物。在sax - 7突变体中，成虫期神经节的组织结构和神经元的定位异常，但在幼虫早期阶段未观察到这些异常。sax - 7突变体中神经元的错位是由与身体运动相关的机械力触发的。在体外聚集试验中，短形式和长形式的SAX - 7分别表现出强和弱的嗜同性黏附活性，这与其在体内的不同活性相关。SAX - 7在体内定位于神经元的质膜上。在sax - 7突变体中仅在单个神经元中表达SAX - 7可自主恢复其正常的神经元位置。在sax - 7突变体的两个不同头部神经元中表达SAX - 7导致这些神经元被迫附着。我们提出，SAX - 7的嗜同性和异嗜性相互作用对于维持有组织神经节中神经元的位置至关重要。
