2022 Fiscal Year Final Research Report
Neurodevelopmental disorder related Rac signaling pathways control the neonatal development of the dentate gyrus
| Project/Area Number |
19K07059
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Institute for Developmental Research Aichi Developmental Disability Center |
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Principal Investigator |
Ito Hidenori 愛知県医療療育総合センター発達障害研究所, 分子病態研究部, 室長 (40311443)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 海馬 / 低分子量Gタンパク質 / 神経細胞 |
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| Outline of Final Research Achievements |
CNKSR2 is a neuronal scaffolding molecule that is encoded by the CNKSR2 gene located on the X chromosome. Variations in the CNKSR2 gene are associated with intellectual disability and epileptic seizures, yet the cellular and molecular roles of CNKSR2 in neuronal development and disease remain poorly characterized. Here, we identify a molecular complex comprising CNKSR2 and the guanine nucleotide exchange factor (GEF) for ARF small GTPases, CYTH2. Our results demonstrate that CNKSR2 and CYTH2 are necessary for the proper development of neonatal mouse dentate granule cells through a mechanism that involves the stabilization of a complex comprising these proteins.
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| Free Research Field |
神経生物学
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| Academic Significance and Societal Importance of the Research Achievements |
知的障害とてんかんを併発するX連鎖知的障害の患者でCNKSR2遺伝子の変異が多数報告されているが、神経系組織における機能や病態との関連についてはよく分かっていなかった。そのような状況下で、私たちは、新生仔期から生後発達期のマウス海馬歯状回神経細胞の発達におけるCNKSR2の機能を明らかにした。この結果は、CNKSR2の新たな分子機能を明らかにするとともに、X連鎖知的障害の病態の一端を明らかにするものであり、疾患治療法開発への端緒となる研究成果であると考えられる。
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