title: 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.
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
authors.forename: Jun-Dal
authors.initials: JD
authors.lastname: Kim
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8572, Japan.
authors.forename: Kyung-Eui
authors.initials: KE
authors.lastname: Park
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ishida
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8572, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kako
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
authors.forename: Juri
authors.initials: J
authors.lastname: Hamada
authors.affiliation: Laboratory for Vertebrate Axis Formation, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kani
authors.affiliation: Laboratory of Organogenesis and Organ Function, Bioscience and Biotechnology Center, Nagoya University, Nagoya, Aichi 464-8601, Japan. ; Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan.
authors.forename: Miki
authors.identifier: 0000-0002-0726-3415
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Namiki
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Fukui
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Fukuhara
authors.affiliation: Laboratory for Vertebrate Axis Formation, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan. ; Laboratory of Organogenesis and Organ Function, Bioscience and Biotechnology Center, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Masahiko
authors.identifier: 0000-0002-9142-4444
authors.initials: M
authors.lastname: Hibi
authors.affiliation: Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kanaho
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Yoshitoshi
authors.initials: Y
authors.lastname: Kasuya
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan. ; AMED-CREST, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan. ; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8572, Japan. ; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
keywords: neurology; vertebrates