Division of Oncology and Division of Neuronal Network, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan, Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan, Laboratory of Molecular Recognition, Graduate School of Arts and Sciences, Yokohama City University, Yokohama 236-0027, Japan, and Cell Signal Unit, Okinawa Institute of Science and Technology, Onna-son, Okinawa 904-0495, Japan.
J Neurosci. 2014 Apr 23;34(17):5927-37. doi: 10.1523/JNEUROSCI.1621-13.2014.
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.
LMTK3 属于 LMTK 蛋白激酶家族，主要在大脑中表达。LMTK3 和中枢神经系统中其他 LMTK 家族成员的生理功能尚不清楚。在这项研究中，我们使用 Lmtk3(-/-) 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，Lmtk3(-/-) 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，我们使用来自 Lmtk3(-/-) 小鼠的培养原代神经元发现，LMTK3 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。受体在 Lmtk3(-/-) 神经元中的膜运输改变可能是突变动物出现行为异常的基础。总之，我们的数据表明 LMTK3 在调节小鼠的运动行为中起着重要作用。
