Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain-Reference-Cited by-同舟云学术

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

Published:2023-05-01 Issue:5 Volume:13 Page:784
ISSN:2218-273X
Container-title:Biomolecules
language:en
Short-container-title:Biomolecules

Author:

Ping Yashuang¹,Ohata Kenji¹²^ORCID,Kikushima Kenji¹³^ORCID,Sakamoto Takumi¹,Islam Ariful¹^ORCID,Xu Lili¹^ORCID,Zhang Hengsen¹,Chen Bin¹,Yan Jing¹,Eto Fumihiro¹^ORCID,Nakane Chiho¹^ORCID,Takao Keizo⁴⁵,Miyakawa Tsuyoshi⁵⁶,Kabashima Katsuya¹^ORCID,Watanabe Miho⁷^ORCID,Kahyo Tomoaki¹³,Yao Ikuko¹³⁸,Fukuda Atsuo⁷^ORCID,Ikegami Koji¹⁹,Konishi Yoshiyuki¹¹⁰^ORCID,Setou Mitsutoshi¹³¹¹^ORCID

Affiliation:

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.

Funder

MEXT Project for promoting public utilization of advanced research infrastructure

AMED

HUSM Grant-in-Aid

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

Link

https://www.mdpi.com/2218-273X/13/5/784/pdf

Reference52 articles.

1. Glutamate as a neurotransmitter in the healthy brain;Zhou;J. Neural Transm.,2014

2. Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain;Zhu;Cell,2018

3. Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration;Andersen;Neuropharmacology,2021

4. Glutamine—A major substrate for nerve endings;Bradford;J. Neurochem.,1978

5. Glutamate as a CNS transmitter. I. Evaluation of glucose and glutamine as precursors for the synthesis of preferentially released glutamate;Hamberger;Brain Res.,1979