Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors

被引:163
作者
Finnemann, SC [1 ]
机构
[1] Cornell Univ, Dyson Vis Res Inst, Dept Ophthalmol, Weill Med Coll, New York, NY 10021 USA
[2] Cornell Univ, Dept Cell & Dev Biol, Weill Med Coll, New York, NY 10021 USA
关键词
focal adhesion kinase; integrins; MerTK; phagocytosis; retinal pigment epithelium;
D O I
10.1093/emboj/cdg416
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Daily alphavbeta5 integrin-dependent phagocytosis of spent photoreceptor outer segment fragments by the retinal pigment epithelium (RPE) is critical for retinal function. This study identifies a key role for focal adhesion kinase (FAK) in RPE phagocytosis. Particle binding increases FAK complex formation with alphavbeta5 receptors at the apical, phagocytic RPE surface and activates FAK. Subsequent particle engulfment coincides with dissociation of activated FAK from alphavbeta5. Mutant FAK retaining focal adhesion targeting but lacking kinase activity interferes with recruitment of full-length FAK to alphavbeta5 and abrogates FAK activation in response to RPE phagocytic challenge. Such inhibition of FAK signaling has no effect on alphavbeta5-dependent binding of particles but blocks their engulfment. Conversely, FAK re-expression promotes particle engulfment by FAK null fibroblasts. Selective ligation of alphavbeta5 receptors at the apical RPE surface is sufficient to phosphorylate and mobilize FAK. Furthermore, FAK phagocytic signaling is independent of the internalization receptor MerTK. In contrast, inhibition of FAK signaling diminishes MerTK phosphorylation. These results demonstrate that FAK provides an essential link between binding and engulfment mechanisms of integrin-mediated phagocytosis.
引用
收藏
页码:4143 / 4154
页数:12
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