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

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

doi:10.3390/biom13050784

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

Biomolecules. 2023 May 1;13(5):784. doi: 10.3390/biom13050784.

Authors

Yashuang Ping¹, Kenji Ohata^{1

2}, Kenji Kikushima^{1

3}, Takumi Sakamoto¹, Ariful Islam¹, Lili Xu¹, Hengsen Zhang¹, Bin Chen¹, Jing Yan¹, Fumihiro Eto¹, Chiho Nakane¹, Keizo Takao^{4

5}, Tsuyoshi Miyakawa^{5

6}, Katsuya Kabashima¹, Miho Watanabe⁷, Tomoaki Kahyo^{1

3}, Ikuko Yao^{1

3

8}, Atsuo Fukuda⁷, Koji Ikegami^{1

9}, Yoshiyuki Konishi^{1

10}, Mitsutoshi Setou^{1

3

11}

Affiliations

¹ Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
² Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
³ International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
⁴ Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
⁵ Genetic Engineering and Functional Genomics Unit, Frontier Technology Center, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
⁶ Institute for Comprehensive Medical Science Division of Systems Medicine, Fujita Health University, Aichi 470-1192, Japan.
⁷ Department of Neurophysiology, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
⁸ Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda, Hyogo 669-1330, Japan.
⁹ Department of Anatomy and Developmental Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima 734-8553, Japan.
¹⁰ Department of Applied Chemistry and Biotechnology, University of Fukui, 3-9-1 Bunkyo, Fukui-shi, Fukui 910-8507, Japan.
¹¹ Department of Systems Molecular Anatomy, Institute for Medical Photonics Research, Preeminent Medical Photonics Education & Research Center, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.

Abstract

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 Ttll1 and Ttll7 knockout mice. Ttll 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.

Keywords: MALDI IMS; TTLL; glutamate; polyglutamylation; post-translational modification; tubulin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / metabolism
Glutamic Acid* / metabolism
Humans
Mice
Mice, Knockout
Neurons / metabolism
Protein Processing, Post-Translational
Tubulin* / metabolism

Substances

Glutamic Acid
Tubulin
tubulin polyglutamylase

Grants and funding

This work was supported by MEXT Project for promoting public utilization of advanced research infrastructure (Imaging Platform), Grant JPMXS0410300222, AMED under Grant JP 21ak010101179, and HUSM Grant-in-Aid.