Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint.
RhoH, an atypical small Rho-family GTPase, critically regulates thymocyte differentiation through the coordinated interaction with Lck and Zap70. Therefore, RhoH deficiency causes defective T cell development, leading to a paucity of mature T cells. Since there has been no gain-of-function study on...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4482576?pdf=render |
| _version_ | 1829503267427581952 |
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| author | Norimasa Tamehiro Hiroyo Oda Mutsunori Shirai Harumi Suzuki |
| author_facet | Norimasa Tamehiro Hiroyo Oda Mutsunori Shirai Harumi Suzuki |
| author_sort | Norimasa Tamehiro |
| collection | DOAJ |
| description | RhoH, an atypical small Rho-family GTPase, critically regulates thymocyte differentiation through the coordinated interaction with Lck and Zap70. Therefore, RhoH deficiency causes defective T cell development, leading to a paucity of mature T cells. Since there has been no gain-of-function study on RhoH before, we decided to take a transgenic approach to assess how the overexpression of RhoH affects the development of T cells. Although RhoH transgenic (RhoHtg) mice expressed three times more RhoH protein than wild-type mice, β-selection, positive, and negative selection in the thymus from RhoHtg mice were unaltered. However, transgenic introduction of RhoH into Rag2 deficient mice resulted in the generation of CD4+ CD8+ (DP) thymocytes, indicating that overexpression of RhoH could bypass β-selection without TCRβ gene rearrangement. This was confirmed by the in vitro development of DP cells from Rag2-/-RhoHtg DN3 cells on TSt-4/Dll-1 stroma in an Lck dependent manner. Collectively, our results indicate that an excess amount of RhoH is able to initiate pre-TCR signaling in the absence of pre-TCR complexes. |
| first_indexed | 2024-12-16T09:55:08Z |
| format | Article |
| id | doaj.art-7ad533a567b04ed1a094cd9ed5d56aea |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T09:55:08Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7ad533a567b04ed1a094cd9ed5d56aea2022-12-21T22:35:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e013104710.1371/journal.pone.0131047Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint.Norimasa TamehiroHiroyo OdaMutsunori ShiraiHarumi SuzukiRhoH, an atypical small Rho-family GTPase, critically regulates thymocyte differentiation through the coordinated interaction with Lck and Zap70. Therefore, RhoH deficiency causes defective T cell development, leading to a paucity of mature T cells. Since there has been no gain-of-function study on RhoH before, we decided to take a transgenic approach to assess how the overexpression of RhoH affects the development of T cells. Although RhoH transgenic (RhoHtg) mice expressed three times more RhoH protein than wild-type mice, β-selection, positive, and negative selection in the thymus from RhoHtg mice were unaltered. However, transgenic introduction of RhoH into Rag2 deficient mice resulted in the generation of CD4+ CD8+ (DP) thymocytes, indicating that overexpression of RhoH could bypass β-selection without TCRβ gene rearrangement. This was confirmed by the in vitro development of DP cells from Rag2-/-RhoHtg DN3 cells on TSt-4/Dll-1 stroma in an Lck dependent manner. Collectively, our results indicate that an excess amount of RhoH is able to initiate pre-TCR signaling in the absence of pre-TCR complexes.http://europepmc.org/articles/PMC4482576?pdf=render |
| spellingShingle | Norimasa Tamehiro Hiroyo Oda Mutsunori Shirai Harumi Suzuki Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint. PLoS ONE |
| title | Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint. |
| title_full | Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint. |
| title_fullStr | Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint. |
| title_full_unstemmed | Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint. |
| title_short | Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint. |
| title_sort | overexpression of rhoh permits to bypass the pre tcr checkpoint |
| url | http://europepmc.org/articles/PMC4482576?pdf=render |
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