Characterization of a novel RP2-OSTF1 interaction and its implication for actin remodeling

Rodanthi Lyraki, Mandy Lokaj, Dinesh C Soares, Abigail Little, Matthieu Vermeren, Joseph A Marsh, Alfred Wittinghofer, Toby Hurd

Research output: Contribution to journalArticlepeer-review

Abstract

Retinitis pigmentosa 2 (RP2) is the causative gene for a form of X-linked retinal degeneration. RP2 was previously shown to have GAP activity towards the small GTPase ARL3 via its N-terminus, but the function of the C-terminus remains elusive. Here, we report a novel interaction between RP2 and Osteoclast-stimulating factor 1 (OSTF1), an intracellular protein that indirectly enhances osteoclast formation and activity and is a negative regulator of cell motility. Moreover, this interaction is abolished by a human pathogenic mutation in RP2. We utilized a structure-based approach to pinpoint the binding interface to a strictly conserved cluster of residues on the surface of RP2 that spans both the C- and N- terminal domains of the protein, and which is structurally distinct from the ARL3 binding site. In addition, we show that RP2 is a positive regulator of cell motility in vitro, recruiting OSTF1 to the cell membrane and preventing its interaction with the migration regulator Myo1E.

Original languageEnglish
JournalJournal of Cell Science
Early online date12 Jan 2018
DOIs
Publication statusE-pub ahead of print - 12 Jan 2018

Keywords

  • Journal Article

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