Serine/Threonine phosphatase PP1 is a regulator of Notch signalling.
- 1Centre For DNA Fingerprinting and Diagnostics, Hyderabad
Abstract
Cell diversity generation is cardinal to the development of the functional central nervous system. The Notch pathway plays an important role in neurogenesis, spanning cell fate determination, cell death, and neural stem cell (NSC) competence switching, and is therefore highly regulated within cells. While the phosphorylation-based regulation of the pathway and its associated kinases is known, few phosphatases have been identified to counterbalance these regulations. Protein Phosphatase 1 is a member of a Serine/Threonine family of phosphatases responsible for a large majority of dephosphorylation events in the cell. In this study, we identify PP1- and its regulatory subunit, PNUTS, as novel regulators of the Notch signalling pathway during Drosophila neurogenesis. We show that PP1-87B/PNUTS positively regulate Notch signalling by dephosphorylating a highly conserved Serine residue in Su(H) to restore its DNA binding activity and thereby activating Notch downstream targets during neurogenesis. This facilitates the execution of two distinct physiological events, NSC apoptosis and competence switching, in different regions of the Drosophila CNS. We find that this regulation of the Notch pathway is also extendable to another cellular context, epithelial wing disc tissue, and critically relies on the phosphatase activity of PP1. Given that we can rescue the Notch-dependent depletion phenotypes of PP1- using its human ortholog, we believe this regulation is likely to be conserved across species during development.
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BibTeX
@misc{barman2026serinethreonine,
title = {{Serine/Threonine phosphatase PP1 is a regulator of Notch signalling.}},
author = {J. Barman and A. Bakshi and R. Sipani and R. JOSHI},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752308},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752308v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Serine/Threonine phosphatase PP1 is a regulator of Notch signalling.
AU - J. Barman
AU - A. Bakshi
AU - R. Sipani
AU - R. JOSHI
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752308
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752308v1
AB - Cell diversity generation is cardinal to the development of the functional central nervous system. The Notch pathway plays an important role in neurogenesis, spanning cell fate determination, cell death, and neural stem cell (NSC) competence switching, and is therefore highly regulated within cells. While the phosphorylation-based regulation of the pathway and its associated kinases is known, few phosphatases have been identified to counterbalance these regulations. Protein Phosphatase 1 is a member of a Serine/Threonine family of phosphatases responsible for a large majority of dephosphorylation events in the cell. In this study, we identify PP1- and its regulatory subunit, PNUTS, as novel regulators of the Notch signalling pathway during Drosophila neurogenesis. We show that PP1-87B/PNUTS positively regulate Notch signalling by dephosphorylating a highly conserved Serine residue in Su(H) to restore its DNA binding activity and thereby activating Notch downstream targets during neurogenesis. This facilitates the execution of two distinct physiological events, NSC apoptosis and competence switching, in different regions of the Drosophila CNS. We find that this regulation of the Notch pathway is also extendable to another cellular context, epithelial wing disc tissue, and critically relies on the phosphatase activity of PP1. Given that we can rescue the Notch-dependent depletion phenotypes of PP1- using its human ortholog, we believe this regulation is likely to be conserved across species during development.
ER -