The Retinal Pigment Epithelium (RPE) makes up the outermost layer of the retina and performs critical photoreceptor-support functions. These functions of RPE require a characteristic apical distribution of certain proteins that are usually targeted basolaterally in other epithelia. Extracellular matrix metalloproteinases inducer, EMMPRIN is one of the proteins that exhibits reversed polarity in adult RPE. In EMMPRTh4 knockout mice, photoreceptors fail to mature, with retinal degeneration ensuing, implying the importance of EMMPRIN in RPE functions. Goal of our proposal is to elucidate the mechanistic involvement of EMMPRIN in RPE functions. Focus of our studies will be to identify EMMPRIN-interacting retinal proteins using yeast two-hybrid system, 'far-western technique' and chemical cross-linkers. In addition, we will study EMMIPRIN's function as dictated by its polarized localization. Functions include matrix metalloproteinase secretion and phagocytosis of photoreceptor outers segments by RPE. A decreased ability of RPE to perform any of its functions may contribute to many inherited and acquired retinal degenerations. Thus, mechanistic studies which aid in understanding of RPE functions would provide pharmacological targets for retinal disorders.
| Deora, Ami A; Philp, Nancy; Hu, Jane et al. (2005) Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia. Proc Natl Acad Sci U S A 102:16245-50 |
| Deora, Ami A; Gravotta, Diego; Kreitzer, Geri et al. (2004) The basolateral targeting signal of CD147 (EMMPRIN) consists of a single leucine and is not recognized by retinal pigment epithelium. Mol Biol Cell 15:4148-65 |
