Focal adhesion kinase signaling promotes phagocytosis of integrin‐bound photoreceptors
Open accessAbstract
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.
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FAK appears to be the bridging step between OS recognition by αvβ5 integrin and OS engulfment mediated by MERTK.
“Focal adhesion kinase (FAK) appears to be the bridging step between OS recognition by αvβ5 integrin and OS engulfment mediated by MERTK (Finnemann, 2003).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Finnemann, 2003
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- Authors
- Finnemann, S. C.
- Affiliations
- Cornell University (US)
- Corresponding author
- Finnemann, Silvia C.
- ORCID
- Finnemann, Silvia C.
- Venue
- The EMBO Journal
- Published
- 2003-08-15
- Volume
- 22
- Issue
- 16
- Pages
- 4143-4154
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC175805
- OpenAlex
- W2048485183
- Cited by
- 208
- References
- 36
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 11 · 2017: 9 · 2016: 5 · 2015: 13 · 2014: 13 · 2013: 18 · 2012: 11
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Research to Prevent Blindness
- National Institutes of Health
- National Eye Institute (R01EY013295, R03EY014184)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- focal adhesion kinase, phagocytosis, integrin αvβ5, retinal pigment epithelium, photoreceptor outer segments, MERTK, particle engulfment, FAK phosphorylation, retinal function
- MeSH terms
- c-Mer Tyrosine Kinase, Adenoviridae, Animals, Cell Adhesion, Cell Line, Fibroblasts, Kinetics, Luminescent Proteins, Phagocytosis, Phosphorylation, Photoreceptor Cells, Pigment Epithelium of Eye, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Rats, Mutant Strains, Rod Cell Outer Segment, Transfection, Signal Transduction, Cell Adhesion Molecules, Integrins, Receptors, Vitronectin, Rats, Long-Evans, Receptor Protein-Tyrosine Kinases, Green Fluorescent Proteins, Mice, Rats, Focal Adhesion Protein-Tyrosine Kinases, Focal Adhesion Kinase 1
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