Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1
Axon guidance molecules are critical for neuronal pathfinding because they regulate directionality and growth pace during nervous system development. However, the molecular mechanisms coordinating proper axonal extension and turning are poorly understood. Here, metastasis suppressor 1 (Mtss1), a mem...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/96891 |
| _version_ | 1797217418550968320 |
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| author | Namsuk Kim Yan Li Ri Yu Hyo-Shin Kwon Anji Song Mi-Hee Jun Jin-Young Jeong Ji Hyun Lee Hyun-Ho Lim Mi-Jin Kim Jung-Woong Kim Won-Jong Oh |
| author_facet | Namsuk Kim Yan Li Ri Yu Hyo-Shin Kwon Anji Song Mi-Hee Jun Jin-Young Jeong Ji Hyun Lee Hyun-Ho Lim Mi-Jin Kim Jung-Woong Kim Won-Jong Oh |
| author_sort | Namsuk Kim |
| collection | DOAJ |
| description | Axon guidance molecules are critical for neuronal pathfinding because they regulate directionality and growth pace during nervous system development. However, the molecular mechanisms coordinating proper axonal extension and turning are poorly understood. Here, metastasis suppressor 1 (Mtss1), a membrane protrusion protein, ensured axonal extension while sensitizing axons to the Semaphorin 3E (Sema3E)-Plexin-D1 repulsive cue. Sema3E-Plexin-D1 signaling enhanced Mtss1 expression in projecting striatonigral neurons. Mtss1 localized to the neurite axonal side and regulated neurite outgrowth in cultured neurons. Mtss1 also aided Plexin-D1 trafficking to the growth cone, where it signaled a repulsive cue to Sema3E. Mtss1 ablation reduced neurite extension and growth cone collapse in cultured neurons. Mtss1-knockout mice exhibited fewer striatonigral projections and irregular axonal routes, and these defects were recapitulated in Plxnd1- or Sema3e-knockout mice. These findings demonstrate that repulsive axon guidance activates an exquisite autoregulatory program coordinating both axonal extension and steering during neuronal pathfinding. |
| first_indexed | 2024-04-24T12:01:33Z |
| format | Article |
| id | doaj.art-129a559dddfa4e4cab3dbafd00bf97aa |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-24T12:01:33Z |
| publishDate | 2024-03-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-129a559dddfa4e4cab3dbafd00bf97aa2024-04-08T15:19:55ZengeLife Sciences Publications LtdeLife2050-084X2024-03-011310.7554/eLife.96891Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1Namsuk Kim0https://orcid.org/0000-0001-5043-0293Yan Li1https://orcid.org/0000-0001-5276-1053Ri Yu2Hyo-Shin Kwon3Anji Song4Mi-Hee Jun5Jin-Young Jeong6Ji Hyun Lee7Hyun-Ho Lim8https://orcid.org/0000-0002-5477-5640Mi-Jin Kim9Jung-Woong Kim10Won-Jong Oh11https://orcid.org/0000-0001-8867-7814Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of Korea; Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaDepartment of Life Sciences, Chung-Ang University, Seoul, Republic of KoreaDepartment of Life Sciences, Chung-Ang University, Seoul, Republic of KoreaNeurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Republic of KoreaAxon guidance molecules are critical for neuronal pathfinding because they regulate directionality and growth pace during nervous system development. However, the molecular mechanisms coordinating proper axonal extension and turning are poorly understood. Here, metastasis suppressor 1 (Mtss1), a membrane protrusion protein, ensured axonal extension while sensitizing axons to the Semaphorin 3E (Sema3E)-Plexin-D1 repulsive cue. Sema3E-Plexin-D1 signaling enhanced Mtss1 expression in projecting striatonigral neurons. Mtss1 localized to the neurite axonal side and regulated neurite outgrowth in cultured neurons. Mtss1 also aided Plexin-D1 trafficking to the growth cone, where it signaled a repulsive cue to Sema3E. Mtss1 ablation reduced neurite extension and growth cone collapse in cultured neurons. Mtss1-knockout mice exhibited fewer striatonigral projections and irregular axonal routes, and these defects were recapitulated in Plxnd1- or Sema3e-knockout mice. These findings demonstrate that repulsive axon guidance activates an exquisite autoregulatory program coordinating both axonal extension and steering during neuronal pathfinding.https://elifesciences.org/articles/96891axon guidanceSemaphorin 3EPlexin-D1Mtss1basal ganglia development |
| spellingShingle | Namsuk Kim Yan Li Ri Yu Hyo-Shin Kwon Anji Song Mi-Hee Jun Jin-Young Jeong Ji Hyun Lee Hyun-Ho Lim Mi-Jin Kim Jung-Woong Kim Won-Jong Oh Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1 eLife axon guidance Semaphorin 3E Plexin-D1 Mtss1 basal ganglia development |
| title | Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1 |
| title_full | Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1 |
| title_fullStr | Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1 |
| title_full_unstemmed | Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1 |
| title_short | Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1 |
| title_sort | repulsive sema3e plexin d1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor mtss1 |
| topic | axon guidance Semaphorin 3E Plexin-D1 Mtss1 basal ganglia development |
| url | https://elifesciences.org/articles/96891 |
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