GIPC proteins negatively modulate Plexind1 signaling during vascular development
Semaphorins (SEMAs) and their Plexin (PLXN) receptors are central regulators of metazoan cellular communication. SEMA-PLXND1 signaling plays important roles in cardiovascular, nervous, and immune system development, and cancer biology. However, little is known about the molecular mechanisms that mod...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/30454 |
| _version_ | 1818028604250914816 |
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| author | Jorge Carretero-Ortega Zinal Chhangawala Shane Hunt Carlos Narvaez Javier Menéndez-González Carl M Gay Tomasz Zygmunt Xiaochun Li Jesús Torres-Vázquez |
| author_facet | Jorge Carretero-Ortega Zinal Chhangawala Shane Hunt Carlos Narvaez Javier Menéndez-González Carl M Gay Tomasz Zygmunt Xiaochun Li Jesús Torres-Vázquez |
| author_sort | Jorge Carretero-Ortega |
| collection | DOAJ |
| description | Semaphorins (SEMAs) and their Plexin (PLXN) receptors are central regulators of metazoan cellular communication. SEMA-PLXND1 signaling plays important roles in cardiovascular, nervous, and immune system development, and cancer biology. However, little is known about the molecular mechanisms that modulate SEMA-PLXND1 signaling. As PLXND1 associates with GIPC family endocytic adaptors, we evaluated the requirement for the molecular determinants of their association and PLXND1’s vascular role. Zebrafish that endogenously express a Plxnd1 receptor with a predicted impairment in GIPC binding exhibit low penetrance angiogenesis deficits and antiangiogenic drug hypersensitivity. Moreover, gipc mutant fish show angiogenic impairments that are ameliorated by reducing Plxnd1 signaling. Finally, GIPC depletion potentiates SEMA-PLXND1 signaling in cultured endothelial cells. These findings expand the vascular roles of GIPCs beyond those of the Vascular Endothelial Growth Factor (VEGF)-dependent, proangiogenic GIPC1-Neuropilin 1 complex, recasting GIPCs as negative modulators of antiangiogenic PLXND1 signaling and suggest that PLXND1 trafficking shapes vascular development. |
| first_indexed | 2024-12-10T05:06:26Z |
| format | Article |
| id | doaj.art-8b95a9a637674fcb8d8850945bec54b5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:06:26Z |
| publishDate | 2019-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8b95a9a637674fcb8d8850945bec54b52022-12-22T02:01:15ZengeLife Sciences Publications LtdeLife2050-084X2019-05-01810.7554/eLife.30454GIPC proteins negatively modulate Plexind1 signaling during vascular developmentJorge Carretero-Ortega0Zinal Chhangawala1Shane Hunt2Carlos Narvaez3Javier Menéndez-González4Carl M Gay5Tomasz Zygmunt6Xiaochun Li7Jesús Torres-Vázquez8https://orcid.org/0000-0002-3808-3978Department of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United StatesDepartment of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United StatesDepartment of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United StatesDepartment of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United StatesDepartment of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United StatesDepartment of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United StatesDepartment of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United StatesDepartment of Population Health, New York University School of Medicine, New York, United StatesDepartment of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United StatesSemaphorins (SEMAs) and their Plexin (PLXN) receptors are central regulators of metazoan cellular communication. SEMA-PLXND1 signaling plays important roles in cardiovascular, nervous, and immune system development, and cancer biology. However, little is known about the molecular mechanisms that modulate SEMA-PLXND1 signaling. As PLXND1 associates with GIPC family endocytic adaptors, we evaluated the requirement for the molecular determinants of their association and PLXND1’s vascular role. Zebrafish that endogenously express a Plxnd1 receptor with a predicted impairment in GIPC binding exhibit low penetrance angiogenesis deficits and antiangiogenic drug hypersensitivity. Moreover, gipc mutant fish show angiogenic impairments that are ameliorated by reducing Plxnd1 signaling. Finally, GIPC depletion potentiates SEMA-PLXND1 signaling in cultured endothelial cells. These findings expand the vascular roles of GIPCs beyond those of the Vascular Endothelial Growth Factor (VEGF)-dependent, proangiogenic GIPC1-Neuropilin 1 complex, recasting GIPCs as negative modulators of antiangiogenic PLXND1 signaling and suggest that PLXND1 trafficking shapes vascular development.https://elifesciences.org/articles/30454angiogenesiscell signalingGIPCPlexinD1Zebrafish |
| spellingShingle | Jorge Carretero-Ortega Zinal Chhangawala Shane Hunt Carlos Narvaez Javier Menéndez-González Carl M Gay Tomasz Zygmunt Xiaochun Li Jesús Torres-Vázquez GIPC proteins negatively modulate Plexind1 signaling during vascular development eLife angiogenesis cell signaling GIPC PlexinD1 Zebrafish |
| title | GIPC proteins negatively modulate Plexind1 signaling during vascular development |
| title_full | GIPC proteins negatively modulate Plexind1 signaling during vascular development |
| title_fullStr | GIPC proteins negatively modulate Plexind1 signaling during vascular development |
| title_full_unstemmed | GIPC proteins negatively modulate Plexind1 signaling during vascular development |
| title_short | GIPC proteins negatively modulate Plexind1 signaling during vascular development |
| title_sort | gipc proteins negatively modulate plexind1 signaling during vascular development |
| topic | angiogenesis cell signaling GIPC PlexinD1 Zebrafish |
| url | https://elifesciences.org/articles/30454 |
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