Centaurin-alpha1 interacts directly with kinesin motor protein KIF13B

J Cell Sci. 2005 Jun 1;118(Pt 11):2471-84. doi: 10.1242/jcs.02369.

Abstract

Centaurin-alpha(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-alpha(1) as bait to identify centaurin-alpha(1) interacting proteins. The yeast two-hybrid screen identified a novel kinesin motor protein as a centaurin-alpha(1) binding partner. The motor protein, termed KIF13B, encoded by a single approximately 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-alpha(1) and KIF13B is direct and mediated by the GAP domain of centaurin-alpha(1) and the stalk domain of KIF13B. Centaurin-alpha(1) and KIF13B form a complex in vivo and the KIF13B interaction appears to be specific to centaurin-alpha(1) as other members of the ARF GAP family did not show any binding activity. We also show that KIF13B and centaurin-alpha(1) colocalize at the leading edges of the cell periphery whereas a deletion mutant of centaurin-alpha(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-alpha(1) in intact cells. Together, our data suggest a mechanism where direct binding between centaurin-alpha(1) and KIF13B could concentrate centaurin-alpha(1) at the leading edges of cells, thus modulating ARF6 function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / metabolism
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • COS Cells
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Chlorocebus aethiops
  • Dogs
  • GTPase-Activating Proteins
  • Gene Library
  • HeLa Cells
  • Humans
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Rats
  • Two-Hybrid System Techniques

Substances

  • ADP-Ribosylation Factor 6
  • Adap1 protein, rat
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • GTPase-Activating Proteins
  • Molecular Motor Proteins
  • Nerve Tissue Proteins
  • KIF13B protein, rat
  • Kinesins
  • ADP-Ribosylation Factors
  • ARF6 protein, human
  • Arf6 protein, rat