Format

Send to

Choose Destination
J Cell Sci. 2018 Feb 20;131(4). pii: jcs211748. doi: 10.1242/jcs.211748.

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

Author information

1
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
2
Structural Biology Group, Max-Planck Institut für Molekulare Physiologie, Abteilung Strukturelle Biologie, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.
3
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
4
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK toby.hurd@igmm.ed.ac.uk.

Abstract

Retinitis pigmentosa 2 (RP2) is the causative gene for a form of X-linked retinal degeneration. RP2 was previously shown to have GTPase-activating protein (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.

KEYWORDS:

Actin; OSTF1; RP2; Retinitis pigmentosa

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center