The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells
Tie1 is a mechanistically poorly characterized endothelial cell (EC)-specific orphan receptor. Yet, Tie1 deletion is embryonic lethal and Tie1 has been implicated in critical vascular pathologies, including atherosclerosis and tumor angiogenesis. Here, we show that Tie1 does not function independent...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715008955 |
| _version_ | 1818062307949805568 |
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| author | Soniya Savant Silvia La Porta Annika Budnik Katrin Busch Junhao Hu Nathalie Tisch Claudia Korn Aida Freire Valls Andrew V. Benest Dorothee Terhardt Xianghu Qu Ralf H. Adams H. Scott Baldwin Carmen Ruiz de Almodóvar Hans-Reimer Rodewald Hellmut G. Augustin |
| author_facet | Soniya Savant Silvia La Porta Annika Budnik Katrin Busch Junhao Hu Nathalie Tisch Claudia Korn Aida Freire Valls Andrew V. Benest Dorothee Terhardt Xianghu Qu Ralf H. Adams H. Scott Baldwin Carmen Ruiz de Almodóvar Hans-Reimer Rodewald Hellmut G. Augustin |
| author_sort | Soniya Savant |
| collection | DOAJ |
| description | Tie1 is a mechanistically poorly characterized endothelial cell (EC)-specific orphan receptor. Yet, Tie1 deletion is embryonic lethal and Tie1 has been implicated in critical vascular pathologies, including atherosclerosis and tumor angiogenesis. Here, we show that Tie1 does not function independently but exerts context-dependent effects on the related receptor Tie2. Tie1 was identified as an EC activation marker that is expressed during angiogenesis by a subset of angiogenic tip and remodeling stalk cells and downregulated in the adult quiescent vasculature. Functionally, Tie1 expression by angiogenic EC contributes to shaping the tip cell phenotype by negatively regulating Tie2 surface presentation. In contrast, Tie1 acts in remodeling stalk cells cooperatively to sustain Tie2 signaling. Collectively, our data support an interactive model of Tie1 and Tie2 function, in which dynamically regulated Tie1 versus Tie2 expression determines the net positive or negative effect of Tie1 on Tie2 signaling. |
| first_indexed | 2024-12-10T14:02:08Z |
| format | Article |
| id | doaj.art-8a8bd19bf7e943c8ba49e7bf3501a59e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T14:02:08Z |
| publishDate | 2015-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8a8bd19bf7e943c8ba49e7bf3501a59e2022-12-22T01:45:46ZengElsevierCell Reports2211-12472015-09-0112111761177310.1016/j.celrep.2015.08.024The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk CellsSoniya Savant0Silvia La Porta1Annika Budnik2Katrin Busch3Junhao Hu4Nathalie Tisch5Claudia Korn6Aida Freire Valls7Andrew V. Benest8Dorothee Terhardt9Xianghu Qu10Ralf H. Adams11H. Scott Baldwin12Carmen Ruiz de Almodóvar13Hans-Reimer Rodewald14Hellmut G. Augustin15Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyDivision of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyDivision of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyDivision of Cellular Immunology, German Cancer Research Center, 69120 Heidelberg, GermanyDivision of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyBiochemistry Center BZH, Heidelberg University, 69120 Heidelberg, GermanyDivision of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyDivision of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyDivision of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyDivision of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyDivision of Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, 48145 Münster, GermanyDivision of Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USABiochemistry Center BZH, Heidelberg University, 69120 Heidelberg, GermanyDivision of Cellular Immunology, German Cancer Research Center, 69120 Heidelberg, GermanyDivision of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, GermanyTie1 is a mechanistically poorly characterized endothelial cell (EC)-specific orphan receptor. Yet, Tie1 deletion is embryonic lethal and Tie1 has been implicated in critical vascular pathologies, including atherosclerosis and tumor angiogenesis. Here, we show that Tie1 does not function independently but exerts context-dependent effects on the related receptor Tie2. Tie1 was identified as an EC activation marker that is expressed during angiogenesis by a subset of angiogenic tip and remodeling stalk cells and downregulated in the adult quiescent vasculature. Functionally, Tie1 expression by angiogenic EC contributes to shaping the tip cell phenotype by negatively regulating Tie2 surface presentation. In contrast, Tie1 acts in remodeling stalk cells cooperatively to sustain Tie2 signaling. Collectively, our data support an interactive model of Tie1 and Tie2 function, in which dynamically regulated Tie1 versus Tie2 expression determines the net positive or negative effect of Tie1 on Tie2 signaling.http://www.sciencedirect.com/science/article/pii/S2211124715008955 |
| spellingShingle | Soniya Savant Silvia La Porta Annika Budnik Katrin Busch Junhao Hu Nathalie Tisch Claudia Korn Aida Freire Valls Andrew V. Benest Dorothee Terhardt Xianghu Qu Ralf H. Adams H. Scott Baldwin Carmen Ruiz de Almodóvar Hans-Reimer Rodewald Hellmut G. Augustin The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells Cell Reports |
| title | The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells |
| title_full | The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells |
| title_fullStr | The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells |
| title_full_unstemmed | The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells |
| title_short | The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells |
| title_sort | orphan receptor tie1 controls angiogenesis and vascular remodeling by differentially regulating tie2 in tip and stalk cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715008955 |
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