| First Author | Yu C | Year | 2019 |
| Journal | J Cell Sci | Volume | 132 |
| Issue | 20 | PubMed ID | 31515275 |
| Mgi Jnum | J:294005 | Mgi Id | MGI:6454435 |
| Doi | 10.1242/jcs.232439 | Citation | Yu C, et al. (2019) Annexin A5 regulates surface alphavbeta5 integrin for retinal clearance phagocytosis. J Cell Sci 132(20):jcs232439 |
| abstractText | Diurnal clearance phagocytosis by the retinal pigment epithelium (RPE) is a conserved efferocytosis process whose binding step is mediated by alphavbeta5 integrin receptors. Two related annexins, A5 (ANXA5) and A6 (ANXA6), share an alphavbeta5 integrin-binding motif. Here, we report that ANXA5, but not ANXA6, regulates the binding capacity for spent photoreceptor outer segment fragments or apoptotic cells by fibroblasts and RPE. Similar to alphavbeta5-deficient RPE, ANXA5(-/-) RPE in vivo lacks the diurnal burst of phagocytosis that follows photoreceptor shedding in wild-type retina. Increasing ANXA5 in cells lacking alphavbeta5 or increasing alphavbeta5 in cells lacking ANXA5 does not affect particle binding. Association of cytosolic ANXA5 and alphavbeta5 integrin in RPE in culture and in vivo further supports their functional interdependence. Silencing ANXA5 is sufficient to reduce levels of alphavbeta5 receptors at the apical phagocytic surface of RPE cells. The effect of ANXA5 on surface alphavbeta5 and on particle binding requires the C-terminal ANXA5 annexin repeat but not its unique N-terminus. These results identify a novel role for ANXA5 specifically in the recognition and binding step of clearance phagocytosis, which is essential to retinal physiology.This article has an associated First Person interview with the first author of the paper. |
