CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans
CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans
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DOI：
10.1073/pnas.0711894105
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发表时间：
2008-04-01
影响因子：
11.1
通讯作者：
Iino, Yuichi
中科院分区：
文献类型：
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作者：
Ikeda, Daisuke D.;Duan, Yukan;Iino, Yuichi
Calsyntenins/alcadeins是一种I型跨膜蛋白，在哺乳动物脑中高度表达，具有两个胞外钙粘蛋白结构域。他们形成了一个三重复合物与X11/X11 L和APP（淀粉样前体蛋白）和蛋白水解加工在一个类似的方式APP。虽然最近有报道的遗传关联的钙结合蛋白-2与人类的记忆性能，在神经系统中的蛋白质的生理作用和分子功能知之甚少。在这里，我们表明，CASY-1，秀丽隐杆线虫的直系同源物的calsyntenins/alcadeins，是必不可少的多种类型的学习。通过遗传筛选，我们发现casy-1突变体在盐趋化性学习中表现出缺陷。casy-1突变体也显示出在温度学习、嗅觉适应和两种感觉信号的整合方面的缺陷。Casy-1在神经系统中广泛表达。casy-1在单个感觉神经元和发育后阶段的表达足以使其在盐趋化性学习中发挥作用。CASY-1的荧光蛋白标记的胞外域从神经元释放。此外，功能结构域分析表明，这种蛋白质的胞质和跨膜结构域是双功能的，而胞外域，其中包含LG/LNS样结构域，是学习所必需的。这些结果表明，学习是由CASY-1的释放胞外域调制。
Calsyntenins/alcadeins are type I transmembrane proteins with two extracellular cadherin domains highly expressed in mammalian brain. They form a tripartite complex with X11/X11L and APP (amyloid precursor protein) and are proteolytically processed in a similar fashion to APP. Although a genetic association of calsyntenin-2 with human memory performance has recently been reported, physiological roles and molecular functions of the protein in the nervous system are poorly understood. Here, we show that CASY-1, the Caenorhabditis elegans ortholog of calsyntenins/alcadeins, is essential for multiple types of learning. Through a genetic screen, we found that casy-1 mutants show defects in salt chemotaxis learning. casy-1 mutants also show defects in temperature learning, olfactory adaptation, and integration of two sensory signals. casy-1 is widely expressed in the nervous system. Expression of casy-1 in a single sensory neuron and at the post-developmental stage is sufficient for its function in salt chemotaxis learning. The fluorescent protein-tagged ectodomain of CASY-1 is released from neurons. Moreover, functional domain analyses revealed that both cytoplasmic and transmembrane domains of this protein are dispensable, whereas the ectodomain, which contains the LG/LNS-like domain, is critically required for learning. These results suggest that learning is modulated by the released ectodomain of CASY-1.