Lowe syndrome–linked endocytic adaptors direct membrane cycling kinetics with OCRL in <i>Dictyostelium discoideum</i>

Luscher, Alexandre; Fröhlich, Florian; Barisch, Caroline; Littlewood, Clare; Metcalfe, Joe; Leuba, Florence; Palma, Anita; Pirruccello, Michelle; Cesareni, Gianni; Stagi, Massimiliano; Walther, Tobias C.; Soldati, Thierry; De Camilli, Pietro; Swan, Laura E.

doi:10.1091/mbc.E18-08-0510

Scientific article

English

Lowe syndrome–linked endocytic adaptors direct membrane cycling kinetics with OCRL in Dictyostelium discoideum

Contributors

Luscher, Alexandre

; Fröhlich, Florian; Barisch, Caroline; Littlewood, Clare; Metcalfe, Joe; Leuba, Florence; Palma, Anita; Pirruccello, Michelle; Cesareni, Gianni; Stagi, Massimiliano; Walther, Tobias C.; Soldati, Thierry

; De Camilli, Pietro; Swan, Laura E.

Published in

Molecular Biology of the Cell, vol. 30, no. 17, p. 2268-2282

Publication date

2019

Abstract

Mutations of the inositol 5-phosphatase OCRL cause Lowe Syndrome (LS), characterized by congenital cataract, low IQ and defective kidney proximal tubule resorption. A key subset of LS mutants abolishes OCRL's interactions with endocytic adaptors containing F&H peptide motifs. Converging unbiased methods examining human peptides and the unicellular phagocytic organism , reveal that, like OCRL, the OCRL orthologue Dd5P4 binds two proteins closely related to the F&H proteins APPL1 and Ses1/2 (also referred to as IPIP27A/B). In addition, a novel conserved F&H interactor was identified, GxcU (in and the Cdc42-GEF Frabin (in human cells). Examining these proteins in , we find that, like OCRL, Dd5P4 acts at well-conserved and physically distinct endocytic stations. Dd5P4 functions in coordination with F&H proteins to control membrane deformation at multiple stages of endocytosis, and suppresses GxcU-mediated activity during fluid-phase micropinocytosis. We also reveal that OCRL/Dd5P4 acts at the contractile vacuole, an exocytic osmoregulatory organelle. We propose F&H peptide-containing proteins may be key modifiers of LS phenotypes.

UNIGE affiliation entities

Faculté des sciences / Section de chimie et biochimie / Département de biochimie

UNIGE research groups

Groupe Soldati

Citation (ISO format)

LUSCHER, Alexandre et al. Lowe syndrome–linked endocytic adaptors direct membrane cycling kinetics with OCRL in Dictyostelium discoideum. In: Molecular Biology of the Cell, 2019, vol. 30, n° 17, p. 2268–2282. doi: 10.1091/mbc.E18-08-0510

Article (Published version)

Article (Submitted version)

Identifiers

PID : unige:136126
DOI : 10.1091/mbc.E18-08-0510

Additional URL for this publication

https://www.molbiolcell.org/doi/10.1091/mbc.E18-08-0510

Journal ISSN

1059-1524

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Creation

21/05/2020 09:11:00

First validation

21/05/2020 09:11:00

Update

13/10/2025 17:22:35

Status update

15/03/2023 21:58:02

Last indexation

07/10/2026 06:38:36