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

Mol Cells. 2021 Mar 31;44(3):168-178. doi: 10.14348/molcells.2021.0027.


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.

Keywords: cell polarity; endosomal sorting complexes required for transport (ESCRT); retinal pigment epithelium (RPE); tumor susceptibility gene 101 (Tsg101).

MeSH terms

  • Animals
  • Cell Polarity / physiology
  • DNA-Binding Proteins / metabolism*
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Epithelial Cells / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism*
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Membrane Proteins
  • Transcription Factors
  • Tsg101 protein