Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation
Abstract Cav3.2 T-type calcium channels are important for the signaling of nociceptive information in the primary afferent pain pathway. During neuropathy and peripheral inflammation, Cav3.2 channels are upregulated due to an increased association with the deubiquitinase USP5. Disrupting these inter...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-10-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13041-018-0405-4 |
| _version_ | 1818479589375082496 |
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| author | Vinicius M. Gadotti Gerald W. Zamponi |
| author_facet | Vinicius M. Gadotti Gerald W. Zamponi |
| author_sort | Vinicius M. Gadotti |
| collection | DOAJ |
| description | Abstract Cav3.2 T-type calcium channels are important for the signaling of nociceptive information in the primary afferent pain pathway. During neuropathy and peripheral inflammation, Cav3.2 channels are upregulated due to an increased association with the deubiquitinase USP5. Disrupting these interactions in male mice by the use of cell permeant peptides reverses mechanical and thermal hypersensitivity. Here we explore the effects of interfering with USP5 binding to the channel in female mice with synchronized estrous cycle. We show that intrathecal delivery of a cell-penetrating TAT peptide corresponding to the UBPc domain of USP5 fully reverses mechanical hypersensitivity in mice intraplantarly injected with Complete Freund’s Adjuvant. Hence, the USP5 mediated dysregulation of Cav3.2 channel activity does not exhibit sex differences, and potential therapeutics targeting this interaction should be effective in both male and female subjects. |
| first_indexed | 2024-12-10T11:12:46Z |
| format | Article |
| id | doaj.art-3c02314b44d94724b055b72e4921802a |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-10T11:12:46Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-3c02314b44d94724b055b72e4921802a2022-12-22T01:51:20ZengBMCMolecular Brain1756-66062018-10-011111310.1186/s13041-018-0405-4Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammationVinicius M. Gadotti0Gerald W. Zamponi1Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute. Cumming School of Medicine, University of CalgaryDepartment of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute. Cumming School of Medicine, University of CalgaryAbstract Cav3.2 T-type calcium channels are important for the signaling of nociceptive information in the primary afferent pain pathway. During neuropathy and peripheral inflammation, Cav3.2 channels are upregulated due to an increased association with the deubiquitinase USP5. Disrupting these interactions in male mice by the use of cell permeant peptides reverses mechanical and thermal hypersensitivity. Here we explore the effects of interfering with USP5 binding to the channel in female mice with synchronized estrous cycle. We show that intrathecal delivery of a cell-penetrating TAT peptide corresponding to the UBPc domain of USP5 fully reverses mechanical hypersensitivity in mice intraplantarly injected with Complete Freund’s Adjuvant. Hence, the USP5 mediated dysregulation of Cav3.2 channel activity does not exhibit sex differences, and potential therapeutics targeting this interaction should be effective in both male and female subjects.http://link.springer.com/article/10.1186/s13041-018-0405-4T-type calcium channelUbiquitinationInflammationPainSex differencesUSP5 |
| spellingShingle | Vinicius M. Gadotti Gerald W. Zamponi Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation Molecular Brain T-type calcium channel Ubiquitination Inflammation Pain Sex differences USP5 |
| title | Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation |
| title_full | Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation |
| title_fullStr | Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation |
| title_full_unstemmed | Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation |
| title_short | Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation |
| title_sort | disrupting usp5 cav3 2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation |
| topic | T-type calcium channel Ubiquitination Inflammation Pain Sex differences USP5 |
| url | http://link.springer.com/article/10.1186/s13041-018-0405-4 |
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