Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure
Robo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mou...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712001623 |
| _version_ | 1811317178378485760 |
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| author | Xueping Fan Qinggang Li Anna Pisarek-Horowitz Hila Milo Rasouly Xiangling Wang Ramon G. Bonegio Hang Wang Margaret McLaughlin Steve Mangos Raghu Kalluri Lawrence B. Holzman Iain A. Drummond Dennis Brown David J. Salant Weining Lu |
| author_facet | Xueping Fan Qinggang Li Anna Pisarek-Horowitz Hila Milo Rasouly Xiangling Wang Ramon G. Bonegio Hang Wang Margaret McLaughlin Steve Mangos Raghu Kalluri Lawrence B. Holzman Iain A. Drummond Dennis Brown David J. Salant Weining Lu |
| author_sort | Xueping Fan |
| collection | DOAJ |
| description | Robo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mouse podocytes and colocalizes with nephrin. Biochemical studies indicate that Robo2 forms a complex with nephrin in the kidney through adaptor protein Nck. In contrast to the role of nephrin that promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization. In addition, the amount of F-actin associated with nephrin is increased in Robo2 knockout mice that develop an altered podocyte foot process structure. Genetic interaction study further reveals that loss of Robo2 alleviates the abnormal podocyte structural phenotype in nephrin null mice. These results suggest that Robo2 signaling acts as a negative regulator on nephrin to influence podocyte foot process architecture. |
| first_indexed | 2024-04-13T12:02:21Z |
| format | Article |
| id | doaj.art-1211909f88b1494e88ef9ad6bb5cba52 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T12:02:21Z |
| publishDate | 2012-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1211909f88b1494e88ef9ad6bb5cba522022-12-22T02:47:44ZengElsevierCell Reports2211-12472012-07-0121526110.1016/j.celrep.2012.06.002Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte StructureXueping Fan0Qinggang Li1Anna Pisarek-Horowitz2Hila Milo Rasouly3Xiangling Wang4Ramon G. Bonegio5Hang Wang6Margaret McLaughlin7Steve Mangos8Raghu Kalluri9Lawrence B. Holzman10Iain A. Drummond11Dennis Brown12David J. Salant13Weining Lu14Renal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USARenal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USARenal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USARenal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USARenal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USARenal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USARenal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USACenter for Systems Biology, Program in Membrane Biology and Division of Nephrology, Massachusetts General Hospital, Boston, MA 02114, USACenter for Systems Biology, Program in Membrane Biology and Division of Nephrology, Massachusetts General Hospital, Boston, MA 02114, USADivision of Matrix Biology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USARenal Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USACenter for Systems Biology, Program in Membrane Biology and Division of Nephrology, Massachusetts General Hospital, Boston, MA 02114, USACenter for Systems Biology, Program in Membrane Biology and Division of Nephrology, Massachusetts General Hospital, Boston, MA 02114, USARenal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USARenal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USARobo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mouse podocytes and colocalizes with nephrin. Biochemical studies indicate that Robo2 forms a complex with nephrin in the kidney through adaptor protein Nck. In contrast to the role of nephrin that promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization. In addition, the amount of F-actin associated with nephrin is increased in Robo2 knockout mice that develop an altered podocyte foot process structure. Genetic interaction study further reveals that loss of Robo2 alleviates the abnormal podocyte structural phenotype in nephrin null mice. These results suggest that Robo2 signaling acts as a negative regulator on nephrin to influence podocyte foot process architecture.http://www.sciencedirect.com/science/article/pii/S2211124712001623 |
| spellingShingle | Xueping Fan Qinggang Li Anna Pisarek-Horowitz Hila Milo Rasouly Xiangling Wang Ramon G. Bonegio Hang Wang Margaret McLaughlin Steve Mangos Raghu Kalluri Lawrence B. Holzman Iain A. Drummond Dennis Brown David J. Salant Weining Lu Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure Cell Reports |
| title | Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure |
| title_full | Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure |
| title_fullStr | Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure |
| title_full_unstemmed | Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure |
| title_short | Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure |
| title_sort | inhibitory effects of robo2 on nephrin a crosstalk between positive and negative signals regulating podocyte structure |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712001623 |
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