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Title

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

Authors
Fröhlich, Florian
Littlewood, Clare
Metcalfe, Joe
Palma, Anita
Pirruccello, Michelle
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Published in Molecular Biology of the Cell. 2019, vol. 30, no. 17, p. 2268-2282
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.
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Research group Groupe Soldati
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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 https://archive-ouverte.unige.ch/unige:136126

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Deposited on : 2020-05-25

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