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First published online May 28, 2005
doi: 10.1242/10.1242/jcs.02369

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Centaurin-₁ interacts directly with kinesin motor protein KIF13B

¹ Department of Pharmacology, School of Medical Sciences, The University of Bristol, University Walk, Bristol, BS8 1TD, UK
² Department of Pharmacology, UIC Cancer Center, University of Illinois College of Medicine, 900 S. Ashland Avenue, Chicago, IL 60607, USA

^* Author for correspondence (e-mail: k.venkateswarlu{at}bristol.ac.uk)

Accepted 9 March 2005

Centaurin-₁ is a phosphatidylinositol 3,4,5-trisphosphate binding protein as well as a GTPase activating protein (GAP) for the ADP-ribosylation factor (ARF) family of small GTPases. To further understand its cellular function, we screened a rat brain cDNA library using centaurin-₁ as bait to identify centaurin-₁ interacting proteins. The yeast two-hybrid screen identified a novel kinesin motor protein as a centaurin-₁ binding partner. The motor protein, termed KIF13B, encoded by a single 9.5-kb transcript, is widely expressed with high levels observed in brain and kidney. Yeast two-hybrid and GST pull-down assays showed that the interaction between centaurin-₁ and KIF13B is direct and mediated by the GAP domain of centaurin-₁ and the stalk domain of KIF13B. Centaurin-₁ and KIF13B form a complex in vivo and the KIF13B interaction appears to be specific to centaurin-₁ as other members of the ARF GAP family did not show any binding activity. We also show that KIF13B and centaurin-₁ colocalize at the leading edges of the cell periphery whereas a deletion mutant of centaurin-₁ that lacks the KIF13B binding site, failed to colocalize with KIF13B in vivo. Finally, we demonstrate that KIF13B binding suppresses the ARF6 GAP activity of centaurin-₁ in intact cells. Together, our data suggest a mechanism where direct binding between centaurin-₁ and KIF13B could concentrate centaurin-₁ at the leading edges of cells, thus modulating ARF6 function.

Key words: Centaurin-₁, KIF13B, PI 3-kinase, PtdIns(3,4,5)P₃, ARF6, Trafficking

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