PUBLICATION
A novel role of PRL in regulating epithelial cell density by inducing apoptosis at confluence
- Authors
- Lohani, S., Funato, Y., Akieda, Y., Mizutani, K., Takai, Y., Ishitani, T., Miki, H.
- ID
- ZDB-PUB-211222-5
- Date
- 2021
- Source
- Journal of Cell Science 135(2): (Journal)
- Registered Authors
- Akieda, Yuki
- Keywords
- Apoptosis, Convergent extension, Epithelial cell density, Phosphatase of regenerating liver (PRL), Zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/genetics
- Cell Count
- Dogs
- Humans
- Liver
- Madin Darby Canine Kidney Cells
- Neoplasm Proteins
- Protein Tyrosine Phosphatases*/genetics
- Zebrafish*/genetics
- PubMed
- 34931244 Full text @ J. Cell Sci.
Citation
Lohani, S., Funato, Y., Akieda, Y., Mizutani, K., Takai, Y., Ishitani, T., Miki, H. (2021) A novel role of PRL in regulating epithelial cell density by inducing apoptosis at confluence. Journal of Cell Science. 135(2):.
Abstract
Maintaining proper epithelial cell density is essential for the survival of multicellular organisms. While regulation of cell density through apoptosis is well known, its mechanistic details remain elusive. Here, we report the involvement of membrane-anchored phosphatase of regenerating liver (PRL), originally known for its role in cancer malignancy, in this process. In epithelial MDCK cells, upon confluence, doxycycline-induced expression of PRL upregulated apoptosis, reducing the cell density. This could be circumvented by artificially reducing the cell density via stretching the cell-seeded silicon chamber. Moreover, siRNA-mediated knockdown of endogenous PRL blocked apoptosis, leading to greater cell density. Mechanistically, PRL promoted apoptosis by upregulating the translation of E-cadherin and activating TGF-β pathway. Morpholino-mediated inhibition of PRL expression in zebrafish embryos caused developmental defect with reduced apoptosis and increased epithelial cell density during convergent extension. This study revealed a novel role of PRL in regulating density-dependent apoptosis in vertebrate epithelium.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping