Laboratory of Molecular Neuroscience, Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Minami-osawa, Hachioji, Tokyo, 192-0397, Japan.
Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.
Sci Rep. 2020 Sep 22;10(1):15461. doi: 10.1038/s41598-020-72304-z.
Lemur tail kinase 1 (LMTK1), previously called Apoptosis-Associated Tyrosine Kinase (AATYK), remains an uncharacterized Ser/Thr protein kinase that is predominantly expressed in the brain. It is recently reported that LMTK1A, an isoform of LMTK1, binds to recycling endosomes through its palmitoylation and regulates endosomal trafficking by suppressing the activity of Rab11 small GTPase. In neurons, knockdown or knockout of LMTK1 results in longer axons, greater branching of dendrites and increased number of spines, suggesting that LMTK1 plays a role in neuronal circuit formation. However, its in vivo function remained to be investigated. Here, we examined the brain structures and behaviors of LMTK1 knockout (KO) mice. LMTK1 was expressed in most neurons throughout the brain. The overall brain structure appeared to be normal in LMTK1 KO mice, but the numbers of synapses were increased. LMTK1 KO mice had a slight impairment in memory formation and exhibited distinct psychiatric behaviors such as hyperactivity, impulsiveness and high motor coordination without social interaction deficits. Some of these abnormal behaviors represent core features of attention deficit hyperactive disorder (ADHD), suggesting the possible involvement of LMTK1 in the pathogenesis of ADHD.
Lemur 尾巴激酶 1（LMTK1），以前称为凋亡相关酪氨酸激酶（AATYK），仍然是一种未被描述的 Ser/Thr 蛋白激酶，主要在大脑中表达。最近有报道称，LMTK1A 是 LMTK1 的一种同工型，通过其棕榈酰化作用与再循环内体结合，并通过抑制 Rab11 小 GTPase 的活性来调节内体运输。在神经元中，LMTK1 的敲低或敲除导致轴突更长、树突分支更多和棘突数量增加，表明 LMTK1 在神经元回路形成中发挥作用。然而，其体内功能仍有待研究。在这里，我们研究了 LMTK1 敲除（KO）小鼠的大脑结构和行为。LMTK1 在大脑中的大多数神经元中表达。LMTK1 KO 小鼠的整体大脑结构似乎正常，但突触数量增加。LMTK1 KO 小鼠在记忆形成方面有轻微的障碍，并表现出明显的精神行为，如多动、冲动和高运动协调性，而没有社交互动障碍。这些异常行为中的一些代表了注意力缺陷多动障碍（ADHD）的核心特征，表明 LMTK1 可能参与 ADHD 的发病机制。
