Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain

As an important neurotransmitter, glutamate acts in over 90% of excitatory synapses in the human brain. Its metabolic pathway is complicated, and the glutamate pool in neurons has not been fully elucidated. Tubulin polyglutamylation in the brain is mainly mediated by two tubulin tyrosine ligase-like...

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Main Authors: Yashuang Ping, Kenji Ohata, Kenji Kikushima, Takumi Sakamoto, Ariful Islam, Lili Xu, Hengsen Zhang, Bin Chen, Jing Yan, Fumihiro Eto, Chiho Nakane, Keizo Takao, Tsuyoshi Miyakawa, Katsuya Kabashima, Miho Watanabe, Tomoaki Kahyo, Ikuko Yao, Atsuo Fukuda, Koji Ikegami, Yoshiyuki Konishi, Mitsutoshi Setou
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/5/784
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author Yashuang Ping
Kenji Ohata
Kenji Kikushima
Takumi Sakamoto
Ariful Islam
Lili Xu
Hengsen Zhang
Bin Chen
Jing Yan
Fumihiro Eto
Chiho Nakane
Keizo Takao
Tsuyoshi Miyakawa
Katsuya Kabashima
Miho Watanabe
Tomoaki Kahyo
Ikuko Yao
Atsuo Fukuda
Koji Ikegami
Yoshiyuki Konishi
Mitsutoshi Setou
author_facet Yashuang Ping
Kenji Ohata
Kenji Kikushima
Takumi Sakamoto
Ariful Islam
Lili Xu
Hengsen Zhang
Bin Chen
Jing Yan
Fumihiro Eto
Chiho Nakane
Keizo Takao
Tsuyoshi Miyakawa
Katsuya Kabashima
Miho Watanabe
Tomoaki Kahyo
Ikuko Yao
Atsuo Fukuda
Koji Ikegami
Yoshiyuki Konishi
Mitsutoshi Setou
author_sort Yashuang Ping
collection DOAJ
description As an important neurotransmitter, glutamate acts in over 90% of excitatory synapses in the human brain. Its metabolic pathway is complicated, and the glutamate pool in neurons has not been fully elucidated. Tubulin polyglutamylation in the brain is mainly mediated by two tubulin tyrosine ligase-like (TTLL) proteins, TTLL1 and TTLL7, which have been indicated to be important for neuronal polarity. In this study, we constructed pure lines of <i>Ttll1</i> and <i>Ttll7</i> knockout mice. <i>Ttll</i> knockout mice showed several abnormal behaviors. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analyses of these brains showed increases in glutamate, suggesting that tubulin polyglutamylation by these TTLLs acts as a pool of glutamate in neurons and modulates some other amino acids related to glutamate.
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spelling doaj.art-eabd2093001c42a9ad0e86bd948d79f82023-11-18T00:39:09ZengMDPI AGBiomolecules2218-273X2023-05-0113578410.3390/biom13050784Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice BrainYashuang Ping0Kenji Ohata1Kenji Kikushima2Takumi Sakamoto3Ariful Islam4Lili Xu5Hengsen Zhang6Bin Chen7Jing Yan8Fumihiro Eto9Chiho Nakane10Keizo Takao11Tsuyoshi Miyakawa12Katsuya Kabashima13Miho Watanabe14Tomoaki Kahyo15Ikuko Yao16Atsuo Fukuda17Koji Ikegami18Yoshiyuki Konishi19Mitsutoshi Setou20Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Behavioral Physiology, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, JapanGenetic Engineering and Functional Genomics Unit, Frontier Technology Center, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Neurophysiology, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Neurophysiology, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanAs an important neurotransmitter, glutamate acts in over 90% of excitatory synapses in the human brain. Its metabolic pathway is complicated, and the glutamate pool in neurons has not been fully elucidated. Tubulin polyglutamylation in the brain is mainly mediated by two tubulin tyrosine ligase-like (TTLL) proteins, TTLL1 and TTLL7, which have been indicated to be important for neuronal polarity. In this study, we constructed pure lines of <i>Ttll1</i> and <i>Ttll7</i> knockout mice. <i>Ttll</i> knockout mice showed several abnormal behaviors. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analyses of these brains showed increases in glutamate, suggesting that tubulin polyglutamylation by these TTLLs acts as a pool of glutamate in neurons and modulates some other amino acids related to glutamate.https://www.mdpi.com/2218-273X/13/5/784glutamateTTLLpolyglutamylationtubulinpost-translational modificationMALDI IMS
spellingShingle Yashuang Ping
Kenji Ohata
Kenji Kikushima
Takumi Sakamoto
Ariful Islam
Lili Xu
Hengsen Zhang
Bin Chen
Jing Yan
Fumihiro Eto
Chiho Nakane
Keizo Takao
Tsuyoshi Miyakawa
Katsuya Kabashima
Miho Watanabe
Tomoaki Kahyo
Ikuko Yao
Atsuo Fukuda
Koji Ikegami
Yoshiyuki Konishi
Mitsutoshi Setou
Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain
Biomolecules
glutamate
TTLL
polyglutamylation
tubulin
post-translational modification
MALDI IMS
title Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain
title_full Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain
title_fullStr Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain
title_full_unstemmed Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain
title_short Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain
title_sort tubulin polyglutamylation by ttll1 and ttll7 regulate glutamate concentration in the mice brain
topic glutamate
TTLL
polyglutamylation
tubulin
post-translational modification
MALDI IMS
url https://www.mdpi.com/2218-273X/13/5/784
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