title: Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression.
abstract: Although protein-tyrosine phosphorylation is important for hippocampus-dependent learning, its role in cerebellum-dependent learning remains unclear. We previously found that PTPMEG, a cytoplasmic protein-tyrosine phosphatase expressed in Purkinje cells (PCs), bound to the carboxyl-terminus of the glutamate receptor delta2 via the postsynaptic density-95/discs-large/ZO-1 domain of PTPMEG. In the present study, we generated PTPMEG-knockout (KO) mice, and addressed whether PTPMEG is involved in cerebellar plasticity and cerebellum-dependent learning. The structure of the cerebellum in PTPMEG-KO mice appeared grossly normal. However, we found that PTPMEG-KO mice showed severe impairment in the accelerated rotarod test. These mice also exhibited impairment in rapid acquisition of the cerebellum-dependent delay eyeblink conditioning, in which conditioned stimulus (450-ms tone) and unconditioned stimulus (100-ms periorbital electrical shock) were co-terminated. Moreover, long-term depression at parallel fiber-PC synapses was significantly attenuated in these mice. Developmental elimination of surplus climbing fibers and the physiological properties of excitatory synaptic inputs to PCs appeared normal in PTPMEG-KO mice. These results suggest that tyrosine dephosphorylation events regulated by PTPMEG are important for both motor learning and cerebellar synaptic plasticity.
authors.affiliation: Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kina
authors.forename: Tohru
authors.initials: T
authors.lastname: Tezuka
authors.forename: Shinji
authors.initials: S
authors.lastname: Kusakawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: Sho
authors.initials: S
authors.lastname: Kakizawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Miho
authors.initials: M
authors.lastname: Ohsugi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kiyama
authors.forename: Reiko
authors.initials: R
authors.lastname: Horai
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iino
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.forename: Toshiya
authors.initials: T
authors.lastname: Manabe
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001767:Blinking / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000528:radiation effects; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000502:physiology*; D011597:Psychomotor Performance; D045442:Rotarod Performance Test / Q000379:methods; D013997:Time Factors
chemical_list: D017027:Protein Tyrosine Phosphatases