Journal
MOLECULES AND CELLS
Volume 44, Issue 3, Pages 168-178Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
DOI: 10.14348/molcells.2021.0027
Keywords
required for transport (ESCRT); retinal pigment epithelium; (Tsg101)
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Funding
- National Research Foundation of Korea (NRF) [NRF-2017R1A2B3002862, NRF-2018R1A5A1024261]
- Korean Ministry of Science and ICT (MSIT), South Korea
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The distribution of membrane proteins in RPE varies during different developmental stages, indicating developmental regulation of protein trafficking. Deletion of Tsg101 disrupts RPE polarity, leading to irregular aggregates and non-polarized distribution of cell adhesion proteins and activation of epidermal growth factor receptor signaling, highlighting the importance of ESCRT-mediated protein trafficking for RPE cell polarity development and maintenance.
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.
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