# Drosophila Abi maintains blood cell homeostasis by promoting clathrin-mediated endocytosis of Notch

## TL;DR

This study shows how Drosophila Abi regulates blood cell balance by controlling Notch signaling through endocytosis, with phosphorylation acting as a regulatory switch.

## Contribution

The paper identifies Drosophila Abi as a novel integrator of actin remodeling and Notch signaling via clathrin-mediated endocytosis.

## Key findings

- Drosophila Abi promotes plasmatocyte-to-crystal cell transdifferentiation through Notch signaling.
- Abi recruits WASp and Notch to sites of clathrin-mediated endocytosis.
- Abl phosphorylation inhibits Abi activity, while PTP61F reverses it to maintain blood cell homeostasis.

## Abstract

Park et al. show that Drosophila Abi, a regulator of actin cytoskeletal dynamics, controls blood cell homeostasis by activating Notch signaling through clathrin-mediated receptor endocytosis. This regulatory process is promoted by PTP61F-mediated Abi dephosphorylation but antagonized by Abl-mediated Abi phosphorylation, revealing a reversible phosphorylation switch that integrates actin remodeling, endocytosis, and Notch signaling.

Abl-interactor (Abi) proteins induce actin polymerization by activating Wiskott–Aldrich syndrome protein (WASp) or SCAR/WASP-family verprolin-homologous protein. Loss of mammalian Abi1 causes myeloproliferative neoplasm; however, little is known about how the Abi family of actin-regulatory proteins regulates blood cell homeostasis. Here, we demonstrate that Drosophila Abi promotes plasmatocyte-to-crystal cell transdifferentiation but represses plasmatocyte-to-lamellocyte transdifferentiation through Notch signaling. Consistent with a previously demonstrated role of clathrin-mediated endocytosis (CME) in Notch signaling activation, we find that Abi promotes Notch-CME by recruiting WASp and the Notch receptor to nascent sites of CME. Finally, we demonstrate that CME and crystal cell formation are inhibited by Abelson (Abl)-mediated phosphorylation of Abi but require PTP61F, a phosphatase that reverses this phosphorylation. Our findings identify Abi as a critical integrator of actin remodeling and Notch-CME and reveal opposing roles of Abl and PTP61F in regulating Abi activity to maintain blood cell homeostasis.