Neuroscience: PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination

Jun Dal Kim; Kyung Eui Park; Junji Ishida; Koichiro Kako; Juri Hamada; Shuichi Kani; Miki Takeuchi; Kana Namiki; Hajime Fukui; Shigetomo Fukuhara; Masahiko Hibi; Makoto Kobayashi; Yasunori Kanaho; Yoshitoshi Kasuya; Naoki Mochizuki; Akiyoshi Fukamizu

doi:10.1126/sciadv.1500615

Neuroscience: PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination

Jun Dal Kim, Kyung Eui Park, Junji Ishida, Koichiro Kako, Juri Hamada, Shuichi Kani, Miki Takeuchi, Kana Namiki, Hajime Fukui, Shigetomo Fukuhara, Masahiko Hibi, Makoto Kobayashi, Yasunori Kanaho, Yoshitoshi Kasuya, Naoki Mochizuki, Akiyoshi Fukamizu^*

^*この論文の責任著者

和漢医薬学総合研究所研究開発部門複雑系解析分野

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

47 被引用数 (Scopus)

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The development of vertebrate neurons requires a change in membrane phosphatidylcholine (PC) metabolism. Although PC hydrolysis is essential for enhanced axonal outgrowth mediated by phospholipase D (PLD), less is known about the determinants of PC metabolism on dendritic arborization. We show that protein arginine methyltransferase 8 (PRMT8) acts as a phospholipase that directly hydrolyzes PC, generating choline and phosphatidic acid. We found that PRMT8 knockout mice (prmt8-/-) displayed abnormal motor behaviors, including hindlimb clasping and hyperactivity. Moreover, prmt8-/-mice and TALEN-induced zebrafish prmt8 mutants and morphants showed abnormal phenotypes, including the development of dendritic trees in Purkinje cells and altered cerebellar structure. Choline and acetylcholine levels were significantly decreased, whereas PC levels were increased, in the cerebellum of prmt8-/-mice. Our findings suggest that PRMT8 acts both as an arginine methyltransferase and as a PC-hydrolyzing PLD that is essential for proper neurological functions.

本文言語	英語
論文番号	e1500615
ジャーナル	Science Advances
巻	1
号	11
DOI	https://doi.org/10.1126/sciadv.1500615
出版ステータス	出版済み - 2015/12

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10.1126/sciadv.1500615

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Kim, J. D., Park, K. E., Ishida, J., Kako, K., Hamada, J., Kani, S., Takeuchi, M., Namiki, K., Fukui, H., Fukuhara, S., Hibi, M., Kobayashi, M., Kanaho, Y., Kasuya, Y., Mochizuki, N., & Fukamizu, A. (2015). Neuroscience: PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination. Science Advances, 1(11), 記事 e1500615. https://doi.org/10.1126/sciadv.1500615

@article{a58b3d1e1f754dfd9d3ea87a45310034,

title = "Neuroscience: PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination",

abstract = "The development of vertebrate neurons requires a change in membrane phosphatidylcholine (PC) metabolism. Although PC hydrolysis is essential for enhanced axonal outgrowth mediated by phospholipase D (PLD), less is known about the determinants of PC metabolism on dendritic arborization. We show that protein arginine methyltransferase 8 (PRMT8) acts as a phospholipase that directly hydrolyzes PC, generating choline and phosphatidic acid. We found that PRMT8 knockout mice (prmt8-/-) displayed abnormal motor behaviors, including hindlimb clasping and hyperactivity. Moreover, prmt8-/-mice and TALEN-induced zebrafish prmt8 mutants and morphants showed abnormal phenotypes, including the development of dendritic trees in Purkinje cells and altered cerebellar structure. Choline and acetylcholine levels were significantly decreased, whereas PC levels were increased, in the cerebellum of prmt8-/-mice. Our findings suggest that PRMT8 acts both as an arginine methyltransferase and as a PC-hydrolyzing PLD that is essential for proper neurological functions.",

author = "Kim, {Jun Dal} and Park, {Kyung Eui} and Junji Ishida and Koichiro Kako and Juri Hamada and Shuichi Kani and Miki Takeuchi and Kana Namiki and Hajime Fukui and Shigetomo Fukuhara and Masahiko Hibi and Makoto Kobayashi and Yasunori Kanaho and Yoshitoshi Kasuya and Naoki Mochizuki and Akiyoshi Fukamizu",

note = "Publisher Copyright: {\textcopyright} 2015 The Authors, some rights reserved;.",

year = "2015",

month = dec,

doi = "10.1126/sciadv.1500615",

language = "英語",

volume = "1",

journal = "Science Advances",

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Kim, JD, Park, KE, Ishida, J, Kako, K, Hamada, J, Kani, S, Takeuchi, M, Namiki, K, Fukui, H, Fukuhara, S, Hibi, M, Kobayashi, M, Kanaho, Y, Kasuya, Y, Mochizuki, N & Fukamizu, A 2015, 'Neuroscience: PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination', Science Advances, vol. 1, no. 11, e1500615. https://doi.org/10.1126/sciadv.1500615

TY - JOUR

T1 - Neuroscience

T2 - PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination

AU - Kim, Jun Dal

AU - Park, Kyung Eui

AU - Ishida, Junji

AU - Kako, Koichiro

AU - Hamada, Juri

AU - Kani, Shuichi

AU - Takeuchi, Miki

AU - Namiki, Kana

AU - Fukui, Hajime

AU - Fukuhara, Shigetomo

AU - Hibi, Masahiko

AU - Kobayashi, Makoto

AU - Kanaho, Yasunori

AU - Kasuya, Yoshitoshi

AU - Mochizuki, Naoki

AU - Fukamizu, Akiyoshi

PY - 2015/12

Y1 - 2015/12

N2 - The development of vertebrate neurons requires a change in membrane phosphatidylcholine (PC) metabolism. Although PC hydrolysis is essential for enhanced axonal outgrowth mediated by phospholipase D (PLD), less is known about the determinants of PC metabolism on dendritic arborization. We show that protein arginine methyltransferase 8 (PRMT8) acts as a phospholipase that directly hydrolyzes PC, generating choline and phosphatidic acid. We found that PRMT8 knockout mice (prmt8-/-) displayed abnormal motor behaviors, including hindlimb clasping and hyperactivity. Moreover, prmt8-/-mice and TALEN-induced zebrafish prmt8 mutants and morphants showed abnormal phenotypes, including the development of dendritic trees in Purkinje cells and altered cerebellar structure. Choline and acetylcholine levels were significantly decreased, whereas PC levels were increased, in the cerebellum of prmt8-/-mice. Our findings suggest that PRMT8 acts both as an arginine methyltransferase and as a PC-hydrolyzing PLD that is essential for proper neurological functions.

AB - The development of vertebrate neurons requires a change in membrane phosphatidylcholine (PC) metabolism. Although PC hydrolysis is essential for enhanced axonal outgrowth mediated by phospholipase D (PLD), less is known about the determinants of PC metabolism on dendritic arborization. We show that protein arginine methyltransferase 8 (PRMT8) acts as a phospholipase that directly hydrolyzes PC, generating choline and phosphatidic acid. We found that PRMT8 knockout mice (prmt8-/-) displayed abnormal motor behaviors, including hindlimb clasping and hyperactivity. Moreover, prmt8-/-mice and TALEN-induced zebrafish prmt8 mutants and morphants showed abnormal phenotypes, including the development of dendritic trees in Purkinje cells and altered cerebellar structure. Choline and acetylcholine levels were significantly decreased, whereas PC levels were increased, in the cerebellum of prmt8-/-mice. Our findings suggest that PRMT8 acts both as an arginine methyltransferase and as a PC-hydrolyzing PLD that is essential for proper neurological functions.

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JO - Science Advances

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Neuroscience: PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination

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