βA3/A1-crystallin regulates apical polarity and EGFR endocytosis in retinal pigmented epithelial cells

Autor: Peng Shang, Kenneth Teel, Stacey Hose, Debasish Sinha, Christopher Scott Fitting, Joseph Weiss, Ashwath Jayagopal, Jiang Qian, Imran Ahmed Bhutto, Yuri V. Sergeev, Sayan Ghosh, José-Alain Sahel, James T. Handa, Meysam Yazdankhah, Haitao Liu, Raju V. S. Rajala, Simon C. Watkins, Nadezda A. Stepicheva, J. Samuel Zigler, Austin McCauley, Rhonda Grebe, Anastasia Strizhakova, Gerard A. Lutty
Přispěvatelé: University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Oklahoma (OU), Johns Hopkins University (JHU), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Eye Institute [Bethesda, MD, États-Unis] (NEI), National Institutes of Health [Bethesda] (NIH)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Phosphatidylinositol 4
5-Diphosphate
QH301-705.5
media_common.quotation_subject
Medicine (miscellaneous)
Retinal Pigment Epithelium
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Cellular imaging
Endocytosis
General Biochemistry
Genetics and Molecular Biology
Article
beta-Crystallin A Chain
Imaging
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Ezrin
Cell polarity
Animals
Humans
Phosphatidylinositol
Biology (General)
Phospholipid Transfer Proteins
Phosphorylation
[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Internalization
Phosphatidylinositol transfer protein
Actin
media_common
Mice
Knockout
Chemistry
Epithelial Cells
eye diseases
Cell biology
ErbB Receptors
Cytoskeletal Proteins
030104 developmental biology
sense organs
General Agricultural and Biological Sciences
030217 neurology & neurosurgery
Protein Binding
Zdroj: Communications Biology
Communications Biology, Nature Publishing Group, 2021, 4, pp.850. ⟨10.1038/s42003-021-02386-6⟩
Communications Biology, Vol 4, Iss 1, Pp 1-14 (2021)
ISSN: 2399-3642
Popis: 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.
Shang et al. utilize a conditional Cryba1 knockout mouse model to demonstrate a key role for βA3/A1-crystallin in retinal pigmented epithelium. As a result of βA3/A1-crystallin deficiency, the authors report EGFR endocytosis defects and actin network disruption which leads to polarity disruption and degeneration through PITP β/PLC signaling.
Databáze: OpenAIRE
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