Tsg101 Is Necessary for the Establishment and Maintenance of Mouse Retinal Pigment Epithelial Cell Polarity

Abstract

The retinal pigment epithelium (RPE) forms a monolayer sheet separating the retina and choroid in vertebrate eyes. The polarized nature of RPE is maintained by distributing membrane proteins differentially along apico-basal axis. We found the distributions of these proteins differ in embryonic, post-natal, and mature mouse RPE, suggesting developmental regulation of protein trafficking. Thus, we deleted tumor susceptibility gene 101 ( Tsg101 ), a key component of endosomal sorting complexes required for transport (ESCRT), in embryonic and mature RPE to determine whether ESCRT-mediated endocytic protein trafficking correlated with the establishment and maintenance of RPE polarity. Loss of Tsg101 severely disturbed the polarity of RPE, which forms irregular aggregates exhibiting non-polarized distribution of cell adhesion proteins and activation of epidermal growth factor receptor signaling. These findings suggest that ESCRT-mediated protein trafficking is essential for the development and maintenance of RPE cell polarity.

Wnt/β-Catenin Signaling Pathway Is Necessary for the Specification but Not the Maintenance of the Mouse Retinal Pigment Epithelium

“…In the mouse RPE, Ctnnb1 was mainly detected in the adherens junction (AJ) ( Supplementary Fig. S1 ), which supports the polarized structure and function of many epithelial cells ( Gumbiner, 2005 ; Le et al, 2021 ; Perez-Moreno et al, 2003 ). Moreover, Ctnnb1 dissociates from the AJ and accumulates in the nucleus of the adult mouse RPE during epithelial-to-mesenchymal transition ( Kim et al, 2008 ).…”

“…The immunostaining of mouse embryonic and adult eyes was done as described in previous reports ( Kim et al, 2021 ; Le et al . , 2021 ).…”

Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium

“…S1A ). Moreover, the polarized distributions of β-catenin and ezrin to the basolateral and apical sides ( Le et al, 2021 ), respectively, were recovered in the RPE of Pten -deficient mice fed the ROL-free diet ( Figs. 3A and 3B ).…”

PTPN23 Neurodevelopmental Disorder Presenting With Optic Atrophy and Spasmus Nutans–Like Nystagmus

“…In mice, Ptpn23 is expressed predominantly in the central nervous system, especially in the neuroepithelial lining of the brainstem as well as at the inner side of the optic vesicles (2). Although PTPN23 is involved in ciliogenesis and the maintenance of retinal pigment epithelial cell polarity (3), the structure and function of retinal outer layers were normal in this patient.…”