Structural insights into Reelin function: present and future
Reelin is a neuronal glycoprotein secreted by the Cajal-Retzius cells in marginal regions of the cerebral cortex and the hippocampus where it plays important roles in the control of neuronal migration and the formation of cellular layers during brain development. This 3461 residue-long protein is co...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-05-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00137/full |
| _version_ | 1811270506581590016 |
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| author | Fanomezana Moutse Ranaivoson Fanomezana Moutse Ranaivoson Sventja evon Daake Sventja evon Daake Davide eComoletti Davide eComoletti Davide eComoletti |
| author_facet | Fanomezana Moutse Ranaivoson Fanomezana Moutse Ranaivoson Sventja evon Daake Sventja evon Daake Davide eComoletti Davide eComoletti Davide eComoletti |
| author_sort | Fanomezana Moutse Ranaivoson |
| collection | DOAJ |
| description | Reelin is a neuronal glycoprotein secreted by the Cajal-Retzius cells in marginal regions of the cerebral cortex and the hippocampus where it plays important roles in the control of neuronal migration and the formation of cellular layers during brain development. This 3461 residue-long protein is composed of a signal peptide, an F-spondin-like domain, eight Reelin repeats (RR1-8), and a positively charged sequence at the C-terminus. Biochemical data indicate that the central region of Reelin binds to the low-density lipoprotein receptors ApoER2 and VLDLR, leading to the phosphorylation of the intracellular adaptor protein Dab1. After secretion, Reelin is rapidly degraded in three major fragments, but the functional significance of this degradation is poorly understood. Probably due to its large mass and the complexity of its architecture, the high-resolution, three-dimensional structure of Reelin has never been determined. However, the crystal structures of some of the reelin repeats have been solved, providing important insights into their fold and the interaction with the ApoER2 receptor. This review discusses the current findings on the structure of Reelin and its binding to the ApoER2 and VLDLR receptors, and we discuss some areas where proteomics and structural biology can help understanding Reelin function in brain development and human health. |
| first_indexed | 2024-04-12T22:03:13Z |
| format | Article |
| id | doaj.art-c1ad9b1977ae4bcf8e25ec678fca6b6f |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-12T22:03:13Z |
| publishDate | 2016-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-c1ad9b1977ae4bcf8e25ec678fca6b6f2022-12-22T03:15:02ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022016-05-011010.3389/fncel.2016.00137195519Structural insights into Reelin function: present and futureFanomezana Moutse Ranaivoson0Fanomezana Moutse Ranaivoson1Sventja evon Daake2Sventja evon Daake3Davide eComoletti4Davide eComoletti5Davide eComoletti6CHINJ/RWJMS-Rutgers UniversityCHINJ/RWJMS-Rutgers UniversityCHINJ/RWJMS-Rutgers UniversityCHINJ/RWJMS-Rutgers UniversityCHINJ/RWJMS-Rutgers UniversityCHINJ/RWJMS-Rutgers UniversityCHINJ/RWJMS-Rutgers UniversityReelin is a neuronal glycoprotein secreted by the Cajal-Retzius cells in marginal regions of the cerebral cortex and the hippocampus where it plays important roles in the control of neuronal migration and the formation of cellular layers during brain development. This 3461 residue-long protein is composed of a signal peptide, an F-spondin-like domain, eight Reelin repeats (RR1-8), and a positively charged sequence at the C-terminus. Biochemical data indicate that the central region of Reelin binds to the low-density lipoprotein receptors ApoER2 and VLDLR, leading to the phosphorylation of the intracellular adaptor protein Dab1. After secretion, Reelin is rapidly degraded in three major fragments, but the functional significance of this degradation is poorly understood. Probably due to its large mass and the complexity of its architecture, the high-resolution, three-dimensional structure of Reelin has never been determined. However, the crystal structures of some of the reelin repeats have been solved, providing important insights into their fold and the interaction with the ApoER2 receptor. This review discusses the current findings on the structure of Reelin and its binding to the ApoER2 and VLDLR receptors, and we discuss some areas where proteomics and structural biology can help understanding Reelin function in brain development and human health.http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00137/fullreelinBrain Developmentcortical layersStructure-functionVLDLRApoER2 |
| spellingShingle | Fanomezana Moutse Ranaivoson Fanomezana Moutse Ranaivoson Sventja evon Daake Sventja evon Daake Davide eComoletti Davide eComoletti Davide eComoletti Structural insights into Reelin function: present and future Frontiers in Cellular Neuroscience reelin Brain Development cortical layers Structure-function VLDLR ApoER2 |
| title | Structural insights into Reelin function: present and future |
| title_full | Structural insights into Reelin function: present and future |
| title_fullStr | Structural insights into Reelin function: present and future |
| title_full_unstemmed | Structural insights into Reelin function: present and future |
| title_short | Structural insights into Reelin function: present and future |
| title_sort | structural insights into reelin function present and future |
| topic | reelin Brain Development cortical layers Structure-function VLDLR ApoER2 |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00137/full |
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