Transglutaminase 2 (TG2) is a multifunctional enzyme present in the cytoplasm, the nucleus, or the extracellular milieu in a variety of cell types. Recent reports identify a role for secreted TG2 as a coreceptor for integrins that can regulate integrin function. In the retina, synchronization of the phagocytosis of spent photoreceptor outer segment fragments in a diurnal burst depends on the integrin receptor αvβ5. Localizing to the apical, phagocytic surface of the retinal pigment epithelium (RPE), αvβ5 integrin stimulates a short but vigorous signaling response in the RPE that is required for particle engulfment. While ligation by the secreted integrin ligand MFG-E8 initiates this burst of αvβ5 activity, the molecular mechanisms terminating it are still unknown. To determine if TG2 may be a candidate regulator for αvβ5 integrin in the RPE, we investigated its expression and localization in retinal tissue and in primary RPE cells in culture. We found that TG2 levels in the neural retina are below the limit of immunoblot detection. In contrast, RPE tissue in vivo in wild-type and β5−/− mice and wild-type rat primary RPE in culture express TG2. TG2 localizes to the basolateral aspect of the RPE in the mouse eye. In RPE cells in culture, TG2 localizes to the cytoplasm and to the lateral membrane where it partially overlaps with the adherens junction protein β-catenin. Taken together, αvβ5 integrin-independent TG2 expression and its absence from the apical surface suggest a role for TG2 in the RPE other than interaction with the phagocytic machinery.
Retinal pigment epithelium Retina Integrins Transglutaminase 2 Protein expression Protein localization
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These studies were supported by NIH grant EY-13295 to S.C.F.
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