TY - JOUR
T1 - βA3/A1-crystallin regulates apical polarity and EGFR endocytosis in retinal pigmented epithelial cells
AU - Shang, Peng
AU - Stepicheva, Nadezda
AU - Teel, Kenneth
AU - McCauley, Austin
AU - Fitting, Christopher Scott
AU - Hose, Stacey
AU - Grebe, Rhonda
AU - Yazdankhah, Meysam
AU - Ghosh, Sayan
AU - Liu, Haitao
AU - Strizhakova, Anastasia
AU - Weiss, Joseph
AU - Bhutto, Imran A.
AU - Lutty, Gerard A.
AU - Jayagopal, Ashwath
AU - Qian, Jiang
AU - Sahel, José Alain
AU - Samuel Zigler, J.
AU - Handa, James T.
AU - Sergeev, Yuri
AU - Rajala, Raju V.S.
AU - Watkins, Simon
AU - Sinha, Debasish
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The retinal pigmented epithelium (RPE) is a monolayer of multifunctional cells located at the back of the eye. High membrane turnover and polarization, including formation of actin-based apical microvilli, are essential for RPE function and retinal health. Herein, we demonstrate an important role for βA3/A1-crystallin in RPE. βA3/A1-crystallin deficiency leads to clathrin-mediated epidermal growth factor receptor (EGFR) endocytosis abnormalities and actin network disruption at the apical side that result in RPE polarity disruption and degeneration. We found that βA3/A1-crystallin binds to phosphatidylinositol transfer protein (PITPβ) and that βA3/A1-crystallin deficiency diminishes phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), thus probably decreasing ezrin phosphorylation, EGFR activation, internalization, and degradation. We propose that βA3/A1-crystallin acquired its RPE function before evolving as a structural element in the lens, and that in the RPE, it modulates the PI(4,5)P2 pool through PITPβ/PLC signaling axis, coordinates EGFR activation, regulates ezrin phosphorylation and ultimately the cell polarity.
AB - The retinal pigmented epithelium (RPE) is a monolayer of multifunctional cells located at the back of the eye. High membrane turnover and polarization, including formation of actin-based apical microvilli, are essential for RPE function and retinal health. Herein, we demonstrate an important role for βA3/A1-crystallin in RPE. βA3/A1-crystallin deficiency leads to clathrin-mediated epidermal growth factor receptor (EGFR) endocytosis abnormalities and actin network disruption at the apical side that result in RPE polarity disruption and degeneration. We found that βA3/A1-crystallin binds to phosphatidylinositol transfer protein (PITPβ) and that βA3/A1-crystallin deficiency diminishes phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), thus probably decreasing ezrin phosphorylation, EGFR activation, internalization, and degradation. We propose that βA3/A1-crystallin acquired its RPE function before evolving as a structural element in the lens, and that in the RPE, it modulates the PI(4,5)P2 pool through PITPβ/PLC signaling axis, coordinates EGFR activation, regulates ezrin phosphorylation and ultimately the cell polarity.
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U2 - 10.1038/s42003-021-02386-6
DO - 10.1038/s42003-021-02386-6
M3 - Article
C2 - 34239035
AN - SCOPUS:85109630056
SN - 2399-3642
VL - 4
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 850
ER -