Dgkγ knock-out mice show impairments in cerebellar motor coordination, Ltd, and the dendritic development of purkinje cells through the activation of pkcγ

Tsumagari, Ryosuke; Kakizawa, Sho; Kikunaga, Sakiko; Fujihara, Yoshitaka; Ueda, Shuji; Yamanoue, Minoru; Saito, Naoaki; Ikawa, Masahito; Shirai, Yasuhito

doi:https://doi.org/10.1523/ENEURO.0319-19.2020

Dgkγ knock-out mice show impairments in cerebellar motor coordination, Ltd, and the dendritic development of purkinje cells through the activation of pkcγ

Tsumagari, Ryosuke; Kakizawa, Sho; Kikunaga, Sakiko et al.

eNeuro, 2020, 7(2), 0319-19

Number of Access:817（2025-10-25 01:50 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78551

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Title	Dgkγ knock-out mice show impairments in cerebellar motor coordination, Ltd, and the dendritic development of purkinje cells through the activation of pkcγ
Creator	CreatorName Tsumagari, Ryosuke
	NRID 1000040291059 1000040291059 CreatorName Kakizawa, Sho
	CreatorName Kikunaga, Sakiko
	NRID 1000070578848 1000070578848 CreatorName Fujihara, Yoshitaka
	NRID 1000050379400 1000050379400 CreatorName Ueda, Shuji
	NRID 1000030182596 1000030182596 CreatorName Yamanoue, Minoru
	NRID 1000060178499 1000060178499 CreatorName Saito, Naoaki
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	NRID 1000060263399 1000060263399 CreatorName Shirai, Yasuhito
Subject	Diacylglycerol kinase
	Knock-out mouse
	Long-term depression
	Motor coordination
	Protein kinase C
	Purkinje cells
Description	Tsumagari, R., Kakizawa, S., Kikunaga, S., Fujihara, Y., Ueda, S., Yamanoue, M., . . . Shirai, Y. (2020). Dgkg knock-out mice show impairments in cerebellar motor coordination, ltd, and the dendritic development of purkinje cells through the activation of pkcg. ENeuro, 7(2) doi:10.1523/ENEURO.0319-19.2020
Abstract	Diacylglycerol kinase g (DGKg) regulates protein kinase C (PKC) activity by converting DG to phosphatidic acid (PA). DGKg directly interacts with PKCg and is phosphorylated by PKCg, resulting in the upregulation of lipid kinase activity. PKC dysfunction impairs motor coordination, indicating that the regulation of PKC activity is important for motor coordination. DGKg and PKC are abundantly expressed in cerebellar Purkinje cells. However, the physiological role of DGKg has not been elucidated. Therefore, we developed DGKg knock-out (KO) mice and tested their cerebellar motor coordination. In DGKg KO mice, cerebellar motor coordination and long-term depression (LTD) were impaired, and the dendrites of Purkinje cells from DGKg KO mice were significantly retracted. Interestingly, treatment with the cPKC inhibitor Gö6976 (Gö) rescued the dendritic re-traction of primary cultured Purkinje cells from DGKg KO mice. In contrast, treatment with the PKC activator 12-o-tetradecanoylphorbol 13-acetate (TPA) reduced morphologic alterations in the dendrites of Purkinje cells from wild-type (WT) mice. In addition, we confirmed the upregulation of PKCg activity in the cerebellum of DGKg KO mice and rescued impaired LTD in DGKg KO mice with a PKCg-specific inhibitor. Furthermore, im-pairment of motor coordination observed in DGKg KO mice was rescued in tm1c mice with DGKg reexpres-sion induced by the FLP-flippase recognition target (FRT) recombination system. These results indicate that DGKg is involved in cerebellar LTD and the dendritic development of Purkinje cells through the regulation of PKCg activity, and thus contributes to cerebellar motor coordination.
Publisher	Society for Neuroscience
Source Title	eNeuro
Volume (Issue)	7(2)
Page	0319-19
Date of Issued	2020-02-07
Language	English
Handle URL	https://hdl.handle.net/11094/78551
eISSN	23732822
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1523/ENEURO.0319-19.2020
Relation.isIdenticalTo	PMID 32033984
Access Rights	open access
CopyRight	© 2020 Tsumagari et al. This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	eNeuro. 2020, 7(2), p. 0319-19
DC.title	Dgkγ knock-out mice show impairments in cerebellar motor coordination, Ltd, and the dendritic development of purkinje cells through the activation of pkcγ
DC.creator	Tsumagari, Ryosuke
	Kakizawa, Sho
	Kikunaga, Sakiko
	Fujihara, Yoshitaka
	Ueda, Shuji
	Yamanoue, Minoru
	Saito, Naoaki
	Ikawa, Masahito
	Shirai, Yasuhito
DC.publisher	Society for Neuroscience
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-02-07
DC.identifier	https://doi.org/10.1523/ENEURO.0319-19.2020
DC.subject	Diacylglycerol kinase
	Knock-out mouse
	Long-term depression
	Motor coordination
	Protein kinase C
	Purkinje cells
DC.description	Tsumagari, R., Kakizawa, S., Kikunaga, S., Fujihara, Y., Ueda, S., Yamanoue, M., . . . Shirai, Y. (2020). Dgkg knock-out mice show impairments in cerebellar motor coordination, ltd, and the dendritic development of purkinje cells through the activation of pkcg. ENeuro, 7(2) doi:10.1523/ENEURO.0319-19.2020
DCTERMS.abstract	Diacylglycerol kinase g (DGKg) regulates protein kinase C (PKC) activity by converting DG to phosphatidic acid (PA). DGKg directly interacts with PKCg and is phosphorylated by PKCg, resulting in the upregulation of lipid kinase activity. PKC dysfunction impairs motor coordination, indicating that the regulation of PKC activity is important for motor coordination. DGKg and PKC are abundantly expressed in cerebellar Purkinje cells. However, the physiological role of DGKg has not been elucidated. Therefore, we developed DGKg knock-out (KO) mice and tested their cerebellar motor coordination. In DGKg KO mice, cerebellar motor coordination and long-term depression (LTD) were impaired, and the dendrites of Purkinje cells from DGKg KO mice were significantly retracted. Interestingly, treatment with the cPKC inhibitor Gö6976 (Gö) rescued the dendritic re-traction of primary cultured Purkinje cells from DGKg KO mice. In contrast, treatment with the PKC activator 12-o-tetradecanoylphorbol 13-acetate (TPA) reduced morphologic alterations in the dendrites of Purkinje cells from wild-type (WT) mice. In addition, we confirmed the upregulation of PKCg activity in the cerebellum of DGKg KO mice and rescued impaired LTD in DGKg KO mice with a PKCg-specific inhibitor. Furthermore, im-pairment of motor coordination observed in DGKg KO mice was rescued in tm1c mice with DGKg reexpres-sion induced by the FLP-flippase recognition target (FRT) recombination system. These results indicate that DGKg is involved in cerebellar LTD and the dendritic development of Purkinje cells through the regulation of PKCg activity, and thus contributes to cerebellar motor coordination.
DC.rights	© 2020 Tsumagari et al. This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78551
citation_title	Dgkγ knock-out mice show impairments in cerebellar motor coordination, Ltd, and the dendritic development of purkinje cells through the activation of pkcγ
citation_author	Tsumagari, Ryosuke
	Kakizawa, Sho
	Kikunaga, Sakiko
	Fujihara, Yoshitaka
	Ueda, Shuji
	Yamanoue, Minoru
	Saito, Naoaki
	Ikawa, Masahito
	Shirai, Yasuhito
citation_publisher	Society for Neuroscience
citation_language	English
citation_date	2020-02-07
citation_journal_title	eNeuro
citation_volume	7
citation_issue	2
citation_firstpage	0319-19
citation_doi	https://doi.org/10.1523/ENEURO.0319-19.2020
citation_pmid	32033984
citation_public_url	https://hdl.handle.net/11094/78551

Dgkγ knock-out mice show impairments in cerebellar motor coordination, Ltd, and the dendritic development of purkinje cells through the activation of pkcγ

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