Abstract
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.
Highlights
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
LMTK1 knockout (KO) mice were blotted with anti-LMTK1, a single but slightly broad band was detected at a molecular mass of approximately 250 kDa in wild type (WT)
While this size was much larger than that predicted from the amino acid sequences, 139.5 kDa and 145.5 kDa for the 1,317 and 1,374 amino acids of LMTK1A and LMTK1B (Fig. 1A), respectively, the band was shown to correspond to LMTK1 based on the absence in KO mouse brain (Fig. 1B)
Summary
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. Lemur tail (former tyrosine) kinase 1 (LMTK1) is, as yet, an uncharacterized protein kinase, which was previously called Apoptosis-Associated Tyrosine Kinase (AATYK) because it was isolated from apoptotic myeloid cells and showed amino acid sequence similarity in the kinase domain to receptor-type tyrosine kinase[6]. LMTK2 was isolated as a myosin VI-binding p rotein[15,16] and shown to bind to protein phosphatase-1 and Inhibitor-29,17 These results support their role in the regulation of endosomal function, but their exact mechanism of action remains elusive, with only limited information available to date. LMTK1A negatively regulates axon elongation and dendrite arborization through activation of Rab[11]; knockdown or knockout of LMTK1 (aatk) results in increased neurite o utgrowth[21,22]. Its in vivo functions have not yet been analyzed
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