Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation
The molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-der...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00172/full |
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| author | Xi-Tao Yang Xi-Tao Yang Xi-Tao Yang Guo-Hui Huang Guo-Hui Huang Hong-Jiang Li Hong-Jiang Li Zhao-Liang Sun Zhao-Liang Sun Nan-Jie Xu Nan-Jie Xu Nan-Jie Xu Dong-Fu Feng Dong-Fu Feng |
| author_facet | Xi-Tao Yang Xi-Tao Yang Xi-Tao Yang Guo-Hui Huang Guo-Hui Huang Hong-Jiang Li Hong-Jiang Li Zhao-Liang Sun Zhao-Liang Sun Nan-Jie Xu Nan-Jie Xu Nan-Jie Xu Dong-Fu Feng Dong-Fu Feng |
| author_sort | Xi-Tao Yang |
| collection | DOAJ |
| description | The molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-derived rat NSCs. Reduced Rac1 activity impaired the nuclear translocation of β-catenin, ultimately causing a repression of NSCs proliferation. Porf-2 knockdown enhanced NSCs proliferation but not in the presence of small molecule inhibitors of Rac1 or Wnt. At the same time, the repression of NSCs proliferation caused by Porf-2 overexpression was counteracted by small molecule activators of Rac1 or Wnt. By using a rat optic nerve crush model, we observed that Porf-2 knockdown enhanced the recovery of visual function. In particular, optic nerve injury in rats led to increased Wnt family member 3a (Wnt3a) protein expression, which we found responsible for enhancing Porf-2 knockdown-induced NSCs proliferation. These findings suggest that Porf-2 exerts its inhibitory effect on NSCs proliferation via Rac1-Wnt/β-catenin pathway. Porf-2 may therefore represent and interesting target for optic nerve injury recovery and therapy. |
| first_indexed | 2024-12-14T00:37:38Z |
| format | Article |
| id | doaj.art-a8be9a53bc014b44ae6855a1bd867bf1 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-14T00:37:38Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-a8be9a53bc014b44ae6855a1bd867bf12022-12-21T23:24:33ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-06-011010.3389/fnmol.2017.00172252839Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell ProliferationXi-Tao Yang0Xi-Tao Yang1Xi-Tao Yang2Guo-Hui Huang3Guo-Hui Huang4Hong-Jiang Li5Hong-Jiang Li6Zhao-Liang Sun7Zhao-Liang Sun8Nan-Jie Xu9Nan-Jie Xu10Nan-Jie Xu11Dong-Fu Feng12Dong-Fu Feng13Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai, ChinaInstitute of Traumatic Medicine, Shanghai Jiao Tong University School of MedicineShanghai, ChinaDepartment of Interventional Radiotherapy, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai, ChinaDepartment of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai, ChinaInstitute of Traumatic Medicine, Shanghai Jiao Tong University School of MedicineShanghai, ChinaDepartment of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai, ChinaInstitute of Traumatic Medicine, Shanghai Jiao Tong University School of MedicineShanghai, ChinaDepartment of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai, ChinaInstitute of Traumatic Medicine, Shanghai Jiao Tong University School of MedicineShanghai, ChinaNeuroscience Division, Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of MedicineShanghai, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of MedicineShanghai, ChinaKey Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineShanghai, ChinaDepartment of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai, ChinaInstitute of Traumatic Medicine, Shanghai Jiao Tong University School of MedicineShanghai, ChinaThe molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-derived rat NSCs. Reduced Rac1 activity impaired the nuclear translocation of β-catenin, ultimately causing a repression of NSCs proliferation. Porf-2 knockdown enhanced NSCs proliferation but not in the presence of small molecule inhibitors of Rac1 or Wnt. At the same time, the repression of NSCs proliferation caused by Porf-2 overexpression was counteracted by small molecule activators of Rac1 or Wnt. By using a rat optic nerve crush model, we observed that Porf-2 knockdown enhanced the recovery of visual function. In particular, optic nerve injury in rats led to increased Wnt family member 3a (Wnt3a) protein expression, which we found responsible for enhancing Porf-2 knockdown-induced NSCs proliferation. These findings suggest that Porf-2 exerts its inhibitory effect on NSCs proliferation via Rac1-Wnt/β-catenin pathway. Porf-2 may therefore represent and interesting target for optic nerve injury recovery and therapy.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00172/fullRhoGAPsPorf-2Wnt/β-catenin pathwayneural stem cellsoptic nerve injury |
| spellingShingle | Xi-Tao Yang Xi-Tao Yang Xi-Tao Yang Guo-Hui Huang Guo-Hui Huang Hong-Jiang Li Hong-Jiang Li Zhao-Liang Sun Zhao-Liang Sun Nan-Jie Xu Nan-Jie Xu Nan-Jie Xu Dong-Fu Feng Dong-Fu Feng Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation Frontiers in Molecular Neuroscience RhoGAPs Porf-2 Wnt/β-catenin pathway neural stem cells optic nerve injury |
| title | Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation |
| title_full | Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation |
| title_fullStr | Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation |
| title_full_unstemmed | Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation |
| title_short | Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation |
| title_sort | rac1 guides porf 2 to wnt pathway to mediate neural stem cell proliferation |
| topic | RhoGAPs Porf-2 Wnt/β-catenin pathway neural stem cells optic nerve injury |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00172/full |
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