Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG.
Tmub1 (C7orf21/HOPS) encodes a protein containing a ubiquitin-like domain. Tmub1 is highly expressed in the nervous system. To study its physiological function, we generated mice with Tmub1 deleted by homologous recombination. The knockout mice were grossly normal and viable. In a comprehensive beha...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2889838?pdf=render |
| _version_ | 1819036890905444352 |
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| author | Wandong Zhang Katerina V Savelieva Adisak Suwanichkul Daniel L Small Laura L Kirkpatrick Nianhua Xu Thomas H Lanthorn Gui-Lan Ye |
| author_facet | Wandong Zhang Katerina V Savelieva Adisak Suwanichkul Daniel L Small Laura L Kirkpatrick Nianhua Xu Thomas H Lanthorn Gui-Lan Ye |
| author_sort | Wandong Zhang |
| collection | DOAJ |
| description | Tmub1 (C7orf21/HOPS) encodes a protein containing a ubiquitin-like domain. Tmub1 is highly expressed in the nervous system. To study its physiological function, we generated mice with Tmub1 deleted by homologous recombination. The knockout mice were grossly normal and viable. In a comprehensive behavioral testing battery, the only knockout phenotype displayed was a strong increase in home cage locomotor activity during the dark phase (subjective day) of the light:dark (L:D) cycle. There were no changes in activity during the light period. There were no changes in locomotor activity observed in other assays, e.g. novel open-field. The increase in dark phase locomotor activity persisted during a seven day D:D (complete darkness) challenge, and remained largely confined to the normally dark period. Telemetric recording in freely moving subjects for one 24 hr L:D cycle, revealed the same increase in locomotor activity in the dark phase. In addition, EEG analysis showed that the knockout mice exhibited increased waking and decreased NREM & REM times during the dark phase, but the EEG was otherwise normal. Using lacZ as a reporter we found Tmub1 expression prominent in a few brain structures including the thalamus, a region known to drive wakefulness and arousal via its projections to the cortex. We identified calcium modulating cyclophilin ligand CAMLG/CAML as a binding partner by a yeast two-hybrid screen of a brain library. The interaction of Tmub1 and CAMLG was confirmed by co-immunoprecipitation assays in HEK cells. The two proteins were also found to be co-localized to the cytoplasm when expressed in HEK cells. Both Tmub1 and CAMLG have been recently described in the regulation of membrane trafficking of specific receptors. Taken together our results implicate Tmub1 in the regulation of locomotor activity and wakefulness and suggest that Tmub1 binds to and functions together with CAMLG. |
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| format | Article |
| id | doaj.art-631edbbabd5b4fbaa44f05a83b203bd5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T08:12:43Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-631edbbabd5b4fbaa44f05a83b203bd52022-12-21T19:10:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0156e1126110.1371/journal.pone.0011261Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG.Wandong ZhangKaterina V SavelievaAdisak SuwanichkulDaniel L SmallLaura L KirkpatrickNianhua XuThomas H LanthornGui-Lan YeTmub1 (C7orf21/HOPS) encodes a protein containing a ubiquitin-like domain. Tmub1 is highly expressed in the nervous system. To study its physiological function, we generated mice with Tmub1 deleted by homologous recombination. The knockout mice were grossly normal and viable. In a comprehensive behavioral testing battery, the only knockout phenotype displayed was a strong increase in home cage locomotor activity during the dark phase (subjective day) of the light:dark (L:D) cycle. There were no changes in activity during the light period. There were no changes in locomotor activity observed in other assays, e.g. novel open-field. The increase in dark phase locomotor activity persisted during a seven day D:D (complete darkness) challenge, and remained largely confined to the normally dark period. Telemetric recording in freely moving subjects for one 24 hr L:D cycle, revealed the same increase in locomotor activity in the dark phase. In addition, EEG analysis showed that the knockout mice exhibited increased waking and decreased NREM & REM times during the dark phase, but the EEG was otherwise normal. Using lacZ as a reporter we found Tmub1 expression prominent in a few brain structures including the thalamus, a region known to drive wakefulness and arousal via its projections to the cortex. We identified calcium modulating cyclophilin ligand CAMLG/CAML as a binding partner by a yeast two-hybrid screen of a brain library. The interaction of Tmub1 and CAMLG was confirmed by co-immunoprecipitation assays in HEK cells. The two proteins were also found to be co-localized to the cytoplasm when expressed in HEK cells. Both Tmub1 and CAMLG have been recently described in the regulation of membrane trafficking of specific receptors. Taken together our results implicate Tmub1 in the regulation of locomotor activity and wakefulness and suggest that Tmub1 binds to and functions together with CAMLG.http://europepmc.org/articles/PMC2889838?pdf=render |
| spellingShingle | Wandong Zhang Katerina V Savelieva Adisak Suwanichkul Daniel L Small Laura L Kirkpatrick Nianhua Xu Thomas H Lanthorn Gui-Lan Ye Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG. PLoS ONE |
| title | Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG. |
| title_full | Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG. |
| title_fullStr | Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG. |
| title_full_unstemmed | Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG. |
| title_short | Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG. |
| title_sort | transmembrane and ubiquitin like domain containing 1 tmub1 regulates locomotor activity and wakefulness in mice and interacts with camlg |
| url | http://europepmc.org/articles/PMC2889838?pdf=render |
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