LMTK3 deficiency causes pronounced locomotor hyperactivity and impairs endocytic trafficking.
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.
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.
Takeshi
T
Inoue
Naosuke
N
Hoshina
Takanobu
T
Nakazawa
Yuji
Y
Kiyama
Shizuka
S
Kobayashi
Takaya
T
Abe
Toshifumi
T
Yamamoto
Toshiya
T
Manabe
Tadashi
T
Yamamoto
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism; D003863:Depression / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics*; D006948:Hyperkinesis / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D017346:Protein Serine-Threonine Kinases; D004298:Dopamine
LMTK; endocytosis; hyperactivity; locomotor; membrane trafficking