Receptor-Like Tyrosine Phosphatase PTP10D Is Required for Long-Term Memory in Drosophila
Receptor-Like Tyrosine Phosphatase PTP10D Is Required for Long-Term Memory in Drosophila
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DOI：
10.1523/jneurosci.4054-06.2007
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发表时间：
2007-04
期刊：
影响因子：
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通讯作者：
Meng Qian;Guohui Pan;Lu Sun;C. Feng;Zuo‐ping Xie;T. Tully;Y. Zhong
中科院分区：
文献类型：
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作者：
Meng Qian;Guohui Pan;Lu Sun;C. Feng;Zuo‐ping Xie;T. Tully;Y. Zhong
酪氨酸磷酸化介导多种信号转导途径，在发育过程和行为可塑性中发挥关键作用。酪氨酸磷酸化水平由蛋白酪氨酸激酶和蛋白酪氨酸磷酸酶（PTP）调节。广泛的研究调查了酪氨酸激酶在记忆形成中的作用。然而，关于 PTP 的研究却很少。迄今为止，仅当小鼠敲除 PTPα（白细胞共同抗原相关蛋白或 PTPδ）时，学习才被证明是有缺陷的。这些研究的一个主要局限性在于它们无法区分记忆形成的急性（生化）损伤和神经发育的慢性异常。通过对长期记忆缺陷的行为筛选，我们发现 chi 突变体会破坏 PTP10D 蛋白酪氨酸磷酸酶基因的表达。我们发现 chi 突变体对于学习、早期记忆和麻醉抵抗记忆来说是正常的，而长期记忆则被特别消除。值得注意的是，在训练前诱导热休克-PTP10D+转基因可以完全挽救chi突变体的记忆缺陷，从而证明PTP10D在行为可塑性中的重要作用。我们发现 PTP10D 在胚胎中枢神经系统和成人大脑中广泛表达。上游激活序列-PTP10D+在蘑菇体中的转基因表达足以挽救chi突变体的记忆缺陷。我们的数据清楚地表明，蘑菇体内通过 PTP10D 发出的信号对于长期记忆的形成至关重要。
Tyrosine phosphorylation mediates multiple signal transduction pathways that play key roles in developmental processes and behavioral plasticity. The level of tyrosine phosphorylation is regulated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Extensive studies have investigated the roles of tyrosine kinases in memory formation. However, there were few studies on PTPs. To date, learning has been shown to be defective only for mouse knock-outs of PTPα, leukocyte common antigen-related, or PTPδ. A major limitation of these studies arises from their inability to distinguish an acute (biochemical) impairment of memory formation from a more chronic abnormality in neurodevelopment. From a behavioral screen for defective long-term memory, we found chi mutants to disrupt expression of the PTP10D protein tyrosine phosphatase gene. We show that chi mutants are normal for learning, early memory, and anesthesia-resistant memory, whereas long-term memory specifically is abolished. Significantly, induction of a heat shock-PTP10D+ transgene before training fully rescues the memory defect of chi mutants, thereby demonstrating an acute role for PTP10D in behavioral plasticity. We show that PTP10D is widely expressed in the embryonic CNS and in the adult brain. Transgenic expression of upstream activating sequence-PTP10D+ in mushroom bodies is sufficient to rescue the memory defect of chi mutants. Our data clearly demonstrate that signaling through PTP10D in mushroom bodies is critical for the formation of long-term memory.