Novel role for alphavbeta5-integrin in retinal adhesion and its diurnal peak.
alpha(v)beta(5)-Integrin is the sole integrin receptor at the retinal pigment epithelium (RPE)-photoreceptor interface and promotes RPE phagocytic signaling to the tyrosine kinase Mer tyrosine kinase (MerTK) once a day in response to circadian photoreceptor shedding. Herein we identify a novel role for alpha(v)beta(5)-integrin in permanent RPE-photoreceptor adhesion that is independent of alpha(v)beta(5)'s function in retinal phagocytosis. To compare retinal adhesion of wild-type and beta(5)-integrin(-/-) mice, we mechanically separated RPE and neural retina and quantified RPE protein and pigment retention with the neural retina. Lack of alpha(v)beta(5)-integrin with normal expression of other RPE integrins greatly weakened retinal adhesion in young mice and accelerated its age-dependent decline. Unexpectedly, the strength of wild-type retinal adhesion varied with a diurnal rhythm that peaked 3.5 h after light onset, after the completion of phagocytosis, when integrin signaling to MerTK is minimal. Permanent alpha(v)beta(5) receptor deficiency attenuated the diurnal peak of retinal adhesion in beta(5)-integrin(-/-) mice. These results identify alpha(v)beta(5)-integrin as the first RPE receptor that contributes to retinal adhesion, a vital mechanism for long-term photoreceptor function and viability. Furthermore, they indicate that alpha(v)beta(5) receptors at the same apical plasma membrane domain of RPE cells fulfill two separate functions that are synchronized by different diurnal rhythms.
Nandrot
Emeline F
EF
Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021, USA.
Anand
Monika
M
Sircar
Mousumi
M
Finnemann
Silvia C
SC
D000818:Animals; D002352:Carrier Proteins; D002448:Cell Adhesion / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000502:physiology; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D019745:cis-trans-Isomerases; D000099149:Ezrin; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D039641:Integrin beta Chains; D016023:Integrins; D021122:Protein Subunits; D019030:Receptors, Vitronectin; D019745:cis-trans-Isomerases; D000099149:Ezrin; D000099178:Retinoid Isomerohydrolase; C064660:integrin alphaVbeta5; C084344:integrin beta5