LMTK3 Deficiency Causes Pronounced Locomotor Hyperactivity and Impairs Endocytic Trafficking
LMTK3 Deficiency Causes Pronounced Locomotor Hyperactivity and Impairs Endocytic Trafficking
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DOI：
10.1523/jneurosci.1621-13.2014
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发表时间：
2014-04-23
影响因子：
5.3
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
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作者：
Inoue, Takeshi;Hoshina, Naosuke;Yamamoto, Tadashi
LMTK 3属于主要在脑中表达的蛋白激酶的LMTK家族。LMTK 3和LMTK家族的其他成员在CNS中的生理功能仍然未知。在这项研究中，我们使用Lmtk 3（-/-）小鼠进行了一系列行为分析，结果表明这些小鼠表现出异常行为，包括明显的运动过度活跃，焦虑行为减少和抑郁样行为减少。同时，与野生型对照相比，Lmtk 3（-/-）小鼠纹状体中的多巴胺代谢物水平和多巴胺周转率增加。此外，使用来自LMTK 3（-/-）小鼠的培养的原代神经元，我们发现LMTK 3参与N-甲基-D-天冬氨酸受体（一种离子型谷氨酸受体）的内吞运输。Lmtk 3（-/-）神经元中受体的膜运输改变可能是突变动物行为异常的基础。总之，我们的数据表明，LMTK 3在调节小鼠的运动行为中起着重要作用。
LMTK3 belongs to the LMTK family of protein kinases that are predominantly expressed in the brain. Physiological functions of LMTK3 and other members of the LMTK family in the CNS remain unknown. In this study, we performed a battery of behavioral analyses using Lmtk3(-/-) mice and showed that these mice exhibit abnormal behaviors, including pronounced locomotor hyperactivity, reduced anxiety behavior, and decreased depression-like behavior. Concurrently, the dopamine metabolite levels and dopamine turnover rate are increased in the striata of Lmtk3(-/-) mice compared with wild-type controls. In addition, using cultured primary neurons from Lmtk3(-/-) mice, we found that LMTK3 is involved in the endocytic trafficking of N-methyl-D-aspartate receptors, a type of ionotropic glutamate receptor. Altered membrane traffic of the receptor in Lmtk3(-/-) neurons may underlie behavioral abnormalities in the mutant animals. Together, our data suggest that LMTK3 plays an important role in regulating locomotor behavior in mice.