title: Plasma membrane protein polarity and trafficking in RPE cells: past, present and future.
abstract: The retinal pigment epithelium (RPE) comprises a monolayer of polarized pigmented epithelial cells that is strategically interposed between the neural retina and the fenestrated choroid capillaries. The RPE performs a variety of vectorial transport functions (water, ions, metabolites, nutrients and waste products) that regulate the composition of the subretinal space and support the functions of photoreceptors (PRs) and other cells in the neural retina. To this end, RPE cells display a polarized distribution of channels, transporters and receptors in their plasma membrane (PM) that is remarkably different from that found in conventional extra-ocular epithelia, e.g. intestine, kidney, and gall bladder. This characteristic PM protein polarity of RPE cells depends on the interplay of sorting signals in the RPE PM proteins and sorting mechanisms and biosynthetic/recycling trafficking routes in the RPE cell. Although considerable progress has been made in our understanding of the RPE trafficking machinery, most available data have been obtained from immortalized RPE cell lines that only partially maintain the RPE phenotype and by extrapolation of data obtained in the prototype Madin-Darby Canine Kidney (MDCK) cell line. The increasing availability of RPE cell cultures that more closely resemble the RPE in vivo together with the advent of advanced live imaging microscopy techniques provides a platform and an opportunity to rapidly expand our understanding of how polarized protein trafficking contributes to RPE PM polarity.
authors.affiliation: Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, 1300 York Ave, New York, NY 100652, USA.
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Lehmann
authors.affiliation: Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, 1300 York Ave, New York, NY 100652, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Benedicto
authors.affiliation: Thomas Jefferson University, Department of Pathology, Anatomy, and Cell Biology, Philadelphia, PA 19107, USA. Electronic address: Nancy.Philp@jefferson.edu.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Philp
authors.affiliation: Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, 1300 York Ave, New York, NY 100652, USA. Electronic address: boulan@med.cornell.edu.
authors.forename: Enrique
authors.initials: E
authors.lastname: Rodriguez-Boulan
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D004285:Dogs; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D021382:Protein Sorting Signals / Q000502:physiology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D021382:Protein Sorting Signals
keywords: RPE culture; clathrin adaptors; retinal pigment epithelium; reversed polarity; sorting signals; stem cells; vectorial transport