High impact information on KIF13B

• Here, we show that the guanylate kinase-like domain of human discs large protein binds directly within the amino acids 607-831 of the stalk domain of GAKIN, a kinesin-like protein of broad distribution [1].
• Overexpression of green fluorescent protein-fused GAKIN in Madin-Darby canine kidney epithelial cells induced long projections with both GAKIN and endogenous discs large accumulating at the tip of these projections [1].
• We propose that the GAKIN-hDlg interaction lays the foundation for a general paradigm of coupling MAGUKs to the microtubule-based cytoskeleton, and that this interaction may be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes in vivo [2].
• Affinity protein purification, peptide sequencing, and cloning of GAKIN cDNA from Jurkat J77 lymphocytes identified GAKIN as a novel member of the kinesin superfamily of motor proteins [2].
• GAKIN sequence contains a motor domain at the NH(2) terminus, a central stalk domain, and a putative microtubule-interacting sequence called the CAP-Gly domain at the COOH terminus [2].

Biological context of KIF13B

• 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 [3].
• We have recently isolated a novel KIF (kinesin) motor protein (KIF13B) that binds to centaurin-alpha1, an ARF6GAP that binds to the second messenger PIP3 [PtdIns(3,4,5)P3] [4].

Physical interactions of KIF13B

• Identification of centaurin-alpha1 as a KIF13B interactor suggests that KIF13B may transport ARF6 and/or PIP3 using centaurin-alpha1 as its receptor [4].
• 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 [3].
• Here we show that a novel protein termed GAKIN binds to the guanylate kinase-like domain of hDlg [2].

Regulatory relationships of KIF13B

• Finally, we demonstrate that KIF13B binding suppresses the ARF6 GAP activity of centaurin-alpha(1) in intact cells [3].

Other interactions of KIF13B

• 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 [3].
• Neuregulin and KIF13B genes, located within this interval, are interesting functional candidate genes for this HSP form [5].

References