Leucine-Rich Repeats and Transmembrane Domain 2 Controls Protein Sorting in the Striatal Projection System and Its Deficiency Causes Disturbances in Motor Responses and Monoamine Dynamic

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Leucine-Rich Repeats and Transmembrane Domain 2 Controls Protein Sorting in the Striatal Projection System and Its Deficiency Causes Disturbances in Motor Responses and Monoamine Dynamic

Material type: 博士論文

Author: 市瀬, 実里

Publisher: Frontiers Media S.A.

Publication date: 2022-06-01

Material Format: Digital

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Name of awarding university/degree: Nagasaki University (長崎大学),博士(医学)

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Note (General)：: The striatum is involved in action selection, and its disturbance can cause movement disorders. Here, we show that leucine-rich repeats and transmembr...

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Material Type: 博士論文
Title: Leucine-Rich Repeats and Transmembrane Domain 2 Controls Protein Sorting in the Striatal Projection System and Its Deficiency Causes Disturbances in Motor Responses and Monoamine Dynamic
Author/Editor: 市瀬, 実里
Author Heading: 市瀬, 実里
Publication, Distribution, etc.: Frontiers Media S.A.
Publication Date: 2022-06-01
Publication Date (W3CDTF): 2022-06-01
Alternative Title: Lrtm2は線条体投射システムにおけるタンパク質の選択的な輸送を制御し、その欠乏は運動機能とモノアミン動態の異常を引き起こす
Periodical title: Frontiers in Molecular Neuroscience
No. or year of volume/issue: 15
Volume: 15
Pages: 856315-
ISSN (Periodical Title): ISSN : 1662-5099
Degree grantor/type: Nagasaki University (長崎大学)
Date Granted: 2022-06-01
Dissertation Number: 甲医歯薬第1456号
Degree Type: 博士(医学)
Text Language Code: eng
Subject Heading: Lrtm2
gene targeting
striatal projection neuron
behavioral abnormality
monoamine metabolism
protein sorting
Target Audience: 一般
Note (General): The striatum is involved in action selection, and its disturbance can cause movement disorders. Here, we show that leucine-rich repeats and transmembrane domain 2 (Lrtm2) controls protein sorting in striatal projection systems, and its deficiency causes disturbances in monoamine dynamics and behavior. The Lrtm2 protein was broadly detected in the brain, but it was enhanced in the olfactory bulb and dorsal striatum. Immunostaining revealed a strong signal in striatal projection output, including GABAergic presynaptic boutons of the SNr. In subcellular fractionation, Lrtm2 was abundantly recovered in the synaptic plasma membrane fraction, synaptic vesicle fraction, and microsome fraction. Lrtm2 KO mice exhibited altered motor responses in both voluntary explorations and forced exercise. Dopamine metabolite content was decreased in the dorsal striatum and hypothalamus, and serotonin turnover increased in the dorsal striatum. The prefrontal cortex showed age-dependent changes in dopamine metabolites. The distribution of glutamate decarboxylase 67 (GAD67) protein and gamma-aminobutyric acid receptor type B receptor 1 (GABABR1) protein was altered in the dorsal striatum. In cultured neurons, wild-type Lrtm2 protein enhanced axon trafficking of GAD67-GFP and GABABR1-GFP whereas such activity was defective in sorting signal-abolished Lrtm2 mutant proteins. The topical expression of hemagglutinin-epitope-tag (HA)-Lrtm2 and a protein sorting signal abolished HALrtm2 mutant differentially affected GABABR1 protein distribution in the dorsal striatum. These results suggest that Lrtm2 is an essential component of striatal projection neurons, contributing to a better understanding of striatal pathophysiology.
長崎大学学位論文学位記番号:博(医歯薬)甲第1456号学位授与年月日:令和4年6月1日
Author: Misato Ichise, Kazuto Sakoori, Kei-ichi Katayama, Naoko Morimura, Kazuyuki Yamada, Hiroki Ozawa, Hayato Matsunaga, Minoru Hatayama, Jun Aruga
Citation: Frontiers in Molecular Neuroscience, 15, art. no. 856315; 2022
identifier:Nagasaki University (長崎大学), 博士(医学) (2022-06-01)
Source: fulltext
https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27484&item_no=1&attribute_id=70&file_no=1
Access Restrictions: インターネット公開
Rights (production): © 2022 Ichise, Sakoori, Katayama, Morimura, Yamada, Ozawa, Matsunaga, Hatayama and Aruga. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Related Material: http://hdl.handle.net/10069/00041586
Related Material (DOI): 10.3389/fnmol.2022.856315
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Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ