Identification of a novel agrin-dependent pathway in cell signaling and adhesion within the erythroid niche
| Autor: | Achille Anselmo, Giovanna D'Amico, Cristina Mazzon, Antonella Viola, E Lauranzano, Adelaida Sarukhan, Cristiana Soldani, Roberta Angioni, C. Ploia |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Erythrocytes Receptor EphB1 Cell Survival Integrin Receptor tyrosine kinase 03 medical and health sciences Mice 0302 clinical medicine hemic and lymphatic diseases Cell Adhesion Animals Agrin Phosphorylation Cell adhesion Molecular Biology LDL-Receptor Related Proteins Megakaryocyte Progenitor Cells Mice Knockout Original Paper biology Cell Biology Erythropoietin-producing hepatocellular (Eph) receptor Adhesion Actin cytoskeleton Cell biology Mice Inbred C57BL 030104 developmental biology Hyaluronan Receptors Microscopy Fluorescence Receptors LDL biology.protein Signal transduction 030217 neurology & neurosurgery Spleen Integrin alpha5beta1 Signal Transduction |
| Zdroj: | Cell Death and Differentiation |
| Popis: | Establishment of cell–cell adhesion is crucial in embryonic development as well as within the stem cell niches of an adult. Adhesion between macrophages and erythroblasts is required for the formation of erythroblastic islands, specialized niches where erythroblasts proliferate and differentiate to produce red blood cells throughout life. The Eph family is the largest known family of receptor tyrosine kinases (RTKs) and controls cell adhesion, migration, invasion and morphology by modulating integrin and adhesion molecule activity and by modifying the actin cytoskeleton. Here, we identify the proteoglycan agrin as a novel regulator of Eph receptor signaling and characterize a novel mechanism controlling cell–cell adhesion and red cell development within the erythroid niche. We demonstrate that agrin induces clustering and activation of EphB1 receptors on developing erythroblasts, leading to the activation of α5β1 integrins. In agreement, agrin knockout mice display severe anemia owing to defective adhesion to macrophages and impaired maturation of erythroid cells. These results position agrin-EphB1 as a novel key signaling couple regulating cell adhesion and erythropoiesis. |
| Databáze: | OpenAIRE |
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