Affiliation |
Faculty of Medicine School of Medicine Department of Medical Sciences, Integrative Physiology |
Title |
Professor |
External Link |
TAKAMIYA Kogo
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Degree 【 display / non-display 】
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博士(医学) ( 1995.3 長崎大学 )
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医学士 ( 1987.3 長崎大学 )
Research Areas 【 display / non-display 】
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Life Science / Cell biology
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Life Science / Neuroscience-general
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Life Science / Medical biochemistry
Papers 【 display / non-display 】
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Wakazono Y., Midorikawa R., Takamiya K.
Neuroscience Research 198 21 - 29 2024.1
Language:English Publishing type:Research paper (scientific journal) Publisher:Neuroscience Research
In the present study, we attempted to temporally and quantitatively analyze the functional contributions of Ca2+-permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) during long-term potentiation (LTP) expression using electrophysiological and pharmacological approaches. In hippocampal CA1 neurons, using 1-naphthyl acetyl spermine (NASPM), a CP-AMPAR antagonist, we began by demonstrating that NASPM-sensitive components, probably including the GluA1 homomer, functionally contributed to about 15% of AMPAR-mediated EPSC amplitude in basal conditions. Then, when NASPM was treated at different time points (3–30 min) after LTP induction, it was found that LTP was almost completely impaired at 3 or 10 min but maintained at 20 or 30 min, although its potentiation was reduced. Further temporal and quantitative analysis revealed that the functional expression of CP-AMPARs began increasing approximately 20 min after LTP induction and reached more than twice the basal level at 30 min. These results suggest that CP-AMPARs in the first 3–10 min of LTP might play an important role in LTP maintenance. Moreover, their decay time was also significantly increased at 30 min, suggesting that CP-AMPARs changed not only quantitatively in LTP but also qualitatively.
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Disordered testosterone transport in mice lacking the ganglioside GM2/GD2 synthase gene Reviewed
Furukawa K., Takamiya K., Ohmi Y., Bhuiyan R.H., Tajima O., Furukawa K.
FEBS Open Bio 13 ( 9 ) 1615 - 1624 2023.9
Language:English Publishing type:Research paper (scientific journal) Publisher:FEBS Open Bio
Genetic disruption of glycosyltransferases has provided clear information on the roles of their reaction products in the body. Our group has studied the function of glycosphingolipids by genetic engineering of glycosyltransferases in cell culture and in mice, which has demonstrated both expected and unexpected results. Among these findings, aspermatogenesis in ganglioside GM2/GD2 synthase knockout mice was one of the most surprising and intriguing results. There were no sperms in testis, and multinuclear giant cells were detected instead of spermatids. Although serum levels of testosterone in the male mice were extremely low, testosterone accumulated in the interstitial tissues, including Leydig cells, and seemed not to be transferred into the seminiferous tubules or vascular cavity from Leydig cells. This was considered to be the cause of aspermatogenesis and low serum levels of testosterone. Patients with a mutant GM2/GD2 synthase gene (SPG26) showed similar clinical signs, not only in terms of the neurological aspects, but also in the male reproductive system. The mechanisms for testosterone transport by gangliosides are discussed here based on our own results and reports from other laboratories.
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Sulistomo HW, Nemoto T, Kage Y, Fujii H, Uchida T, Takamiya K, Sumimoto H, Kataoka H, Bito H, Takeya R
Cerebral cortex (New York, N.Y. : 1991) 31 ( 4 ) 2205 - 2219 2021.3
Language:English Publishing type:Research paper (scientific journal) Publisher:Cerebral Cortex
Changes in the shape and size of the dendritic spines are critical for synaptic transmission. These morphological changes depend on dynamic assembly of the actin cytoskeleton and occur differently in various types of neurons. However, how the actin dynamics are regulated in a neuronal cell type-specific manner remains largely unknown. We show that Fhod3, a member of the formin family proteins that mediate F-actin assembly, controls the dendritic spine morphogenesis of specific subpopulations of cerebrocortical pyramidal neurons. Fhod3 is expressed specifically in excitatory pyramidal neurons within layers II/III and V of restricted areas of the mouse cerebral cortex. Immunohistochemical and biochemical analyses revealed the accumulation of Fhod3 in postsynaptic spines. Although targeted deletion of Fhod3 in the brain did not lead to any defects in the gross or histological appearance of the brain, the dendritic spines in pyramidal neurons within presumptive Fhod3-positive areas were morphologically abnormal. In primary cultures prepared from the Fhod3-depleted cortex, defects in spine morphology were only detected in Fhod3 promoter-active cells, a small population of pyramidal neurons, and not in Fhod3 promoter-negative pyramidal neurons. Thus, Fhod3 plays a crucial role in dendritic spine morphogenesis only in a specific population of pyramidal neurons in a cell type-specific manner.
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Morise,J., Yamamoto, S., Midorikawa,R., Takamiya,K., Nonaka, M., Takematsu H., Oka, S.
International Molecular Science 21 ( 14 ) 1 - 11 2020.7
Language:English Publishing type:Research paper (scientific journal) Publisher:International Journal of Molecular Sciences
The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1–4), and its abundance in the synapse determines the strength of synaptic activity. The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits’ ER-exit and translocation to the cell membrane. Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear. In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions. In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner. Unlike wild-type (WT) GluA1, GluA2WT rescued surface GluA2N370Q expression. Additionally, the expression of GluA1N63Q reduced the cell surface expression level of GluA1WT. In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
DOI: 10.3390/ijms21145101
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Midorikawa R, Takakura D, Morise J, Wakazono Y, Kawasaki N, Oka S, Takamiya K
Journal of neurochemistry 153 ( 5 ) e14964 - 585 2020.1
Language:Japanese Publishing type:Research paper (scientific journal) Publisher:Journal of Neurochemistry
In the mammalian nervous system, protein N-glycosylation plays an important role in neuronal physiology. In this study, we performed a comprehensive N-glycosylation analysis of mouse GluA1, one of the major subunits of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate type glutamate receptor, which possesses six potential N-glycosylation sites in the N-terminal domain. By mass spectrometry-based analysis, we identified the N-glycoforms and semiquantitatively determined the site-specific N-glycosylation occupancy of GluA1. In addition, only the N401-glycosylation site demonstrated incomplete N-glycosylation occupancy. Therefore, we generated a peptide antibody that specifically detects the N401-glycan-free form to precisely quantify N401-glycosylation occupancy. Using this antibody, we clarified that N401 occupancy varies between cell types and increases in an age-dependent manner in mouse forebrains. To address the regulatory mechanism of N401-glycosylation, binding proteins of GluA1 around the N401 site were screened. HSP70 family proteins, including Bip, were identified as candidates. Bip has been known as a molecular chaperone that plays a key role in protein folding in the ER (endoplasmic reticulum). To examine the involvement of Bip in N401-glycosylation, the effect of Bip over-expression on N401 occupancy was evaluated in HEK293T cells, and the results demonstrated Bip increases the N401 glycan-free form by mediating selective prolongation of its protein half-life. Taken together, we propose that the N401-glycosite of GluA1 receives a unique control of modification, and we also propose a novel N-glycosylation occupancy regulatory mechanism by Bip that might be associated with α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors function in the brain. (Figure presented.).
DOI: 10.1111/jnc.14964
MISC 【 display / non-display 】
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高次脳神経機能の分子機構:記憶形成のメカニズムの最近の進歩
高宮考悟
宮崎県内科医会誌 81 3 - 7 2012.3
Language:Japanese Publishing type:Research paper, summary (national, other academic conference) Publisher:宮崎県内科医会
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学習・記憶におけるシナプス可塑性の分子機構
高宮考悟
生化学 83 ( 11 ) 1016 - 1026 2011.11
Language:Japanese Publishing type:Research paper, summary (national, other academic conference) Publisher:(社) 日本生化学会英文誌
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Takamiya Kogo
The Journal of the Miyazaki Medical Association 34 ( 1 ) 1 - 10 2010.2
Language:Japanese Publishing type:Article, review, commentary, editorial, etc. (scientific journal)
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Seol G., Ziburkus J., Huang S., Song L., Kim I., Takamiya K., Huganir R., Lee H., Kirkwood A.
Neuron 56 ( 4 ) 2007.11
Language:Japanese Publishing type:Article, review, commentary, editorial, etc. (bulletin of university, research institution) Publisher:Neuron
Presentations 【 display / non-display 】
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Arsenic and its metabolites affect synaptic plasticity mediated by AMPA type glutamate receptor trafficking in neurons
Yoshihiko Wakazono
第40回日本神経科学大会
Event date: 2017.7.21 - 2017.7.24
Language:English Presentation type:Poster presentation
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N-glycosylation sites are essential for proper tetramer formation and cell surface expression of AMPA-type glutamate receptor
Munal Babu Kandel
第40回日本神経科学大会
Event date: 2017.7.20 - 2017.7.23
Language:English Presentation type:Poster presentation
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N-glycosylation of AMPA receptor regulates its membrane distribution and channel property
Yoshihiko Wakazono
第94回日本整理学会大会
Event date: 2017.3.31
Language:English Presentation type:Poster presentation
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A novel regulatory mechanism of synaptic plasticity mediated by AMPA-type glutamate receptor glycosylation
Kogo Takamiya
2016 International Symposium on Neurodegenerative Diseases & the 43rd Annual Conference of Japan Brain Scinces Society
Event date: 2016.11.10 - 2016.11.12
Language:English Presentation type:Oral presentation (general)
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Two N-glycosylation sites regulate cell surface expression of AMPA-type glutamate receptor in neurons
Munal Babu Kandel
第67回西日本整理学会
Event date: 2016.10.7 - 2016.10.8
Language:English Presentation type:Oral presentation (general)
Grant-in-Aid for Scientific Research 【 display / non-display 】
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GRIA1遺伝子変異が関与する自閉スペクトラム症の病態解明
Grant number:21K07757 2021.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
内田 琢、
Authorship:Coinvestigator(s)
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グルタミン酸受容体の糖鎖修飾による脳高次機能と精神疾患への関与
Grant number:21K07483 2021.04 - 2024.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
Authorship:Principal investigator
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神経シナプス可塑性発現メカニズムの解明
2017.04 - 2020.03
科学研究費補助金 基盤研究(C)
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A novel principal regulatory mechanism of synaptic plasticity by AMPA-type glutamate receptor glycosylation
2016.04 - 2018.03
Grant-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas
Authorship:Principal investigator
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高次脳神経機能におけるシナプス可塑性の神経細胞外微小環境による制御機構の解明
2011.07 - 2016.03
科学研究費補助金 新学術領域研究
Authorship:Principal investigator
高次脳神経機能におけるシナプス可塑性の神経細胞外微小環境による制御機構の解明
Other research activities 【 display / non-display 】
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宮崎痛みを考える会
2016.02
座長
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大学院講義
2011.12
名古屋大学医学部 グローバルCOEプログラム
ニューロサイエンスコース(英語講義) -
大学院講義
2011.10
産業医科大学大学院での講義
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大学院講義
2011.06
島根大学大学院
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大学院講義
2011.01
名古屋大学 グローバルCOE
大学院講義(英語)
Available Technology 【 display / non-display 】
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記憶・学習の基礎となるシナプス可塑性の分子機構
発達障害における脳内メカニズム
神経再生による損傷脳の修復Related fields where technical consultation is available:神経生化学、細胞生物学、分子生物学・初代神経細胞培養、電気生理学、マウスの行動解析・遺伝子改変マウスの作成、解析
脳・神経疾患の発症メカニズムMessage:神経関係の研究には、技術的に幅広い分野において協力できます。