Lack of an intracellular communication protein called LMTK3 causes hyperactivity in mice, researchers in Okinawa have reported. Symptoms of the behavioral disorder hyperactivity include restlessness, lack of coordination, and aggressive behavior.

Among the 60 trillion cells that make up our bodies there is constant communication. Information is relayed as chemical compounds released by certain cells are received by receptors in the membrane of other cells.

The Okinawa Institute of Science and Technology Cell Signal Unit is investigating genetic factors that contribute to disordered behaviors. They seek to help explain the pathological mechanisms underlying autism and Attention Deficit Hyperactivity Disorder, ADHD, in humans.

Lemur Tyrosine Kinase 3

The protein kinase Lemur Tyrosine Kinase 3 (LMTK3) is plentiful in two brain regions. One is the cerebral cortex, which coordinates perception, movement, and thought. The other is the hippocampus, which governs memory and learning.

In the brain, neurons communicate via connections called synapses. To send a message, a nerve terminus in the pre-synapse releases neurotransmitters, to be received by the post-synaptic receptors. Professor Tadashi Yamamoto’s team at OIST found that LMTK3 regulates the trafficking of neurotransmitter receptors at synapses.

In the neurons of mice lacking LMTK3, internalization of receptors are increased in the post-synapse, hinting that synaptic communication is impaired. The LMTK3-deficient mice showed assorted hyperactive behaviors like restlessness and hypersensitivity to sound. Interestingly, their dopamine levels were elevated.

Dopamine Activity

Dopamine is a neurotransmitter known to be associated with the regulation of movement and learning, hormone levels, motivation, and emotional expression. Excessive dopamine secretion results in schizophrenia, causing a loss of integrity of neuronal activity, and abnormal thoughts and emotions.

However, the links between regulation of neurotransmitter receptor expression by LMTK3, dopamine turnover, and the biochemical pathways that induce hyperactivity, remain a mystery. Actually, the functions of many human proteins are still not understood.

“We hope to advance our research in order to elucidate genetic defects that result in behavioral abnormalities,” said Professor Yamamoto.

The OIST Cell Signal Unit continues genetic studies of intracellular proteins that maintain and regulate complex functions such as behaviors, through their activities inside cells.

T. Inoue, N. Hoshina, T. Nakazawa, Y. Kiyama, S. Kobayashi, T. Abe, T. Yamamoto, T. Manabe, T. Yamamoto. LMTK3 Deficiency Causes Pronounced Locomotor Hyperactivity and Impairs Endocytic Trafficking. Journal of Neuroscience, 2014; 34 (17): 5927 DOI: 10.1523/JNEUROSCI.1621-13.2014

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