The human mitotic kinesin KIF18A binds protein phosphatase 1 (PP1) through a highly conserved docking motif

• The mitotic kinesin-8 family member KIF18A was demonstrated to be a direct PP1 binding partner.
• KIF18A docks PP1 through a classic RVxF binding motif.
• KIF18A preferentially binds the PP1γ isoform.
• The PP1 binding motif is remarkably conserved across eukaryotic KIF18A members, but not in other kinesin-8 family members.
• KIF18A and PP1 co-localize at the outer kinetochore during mitosis.

Protein phosphatase 1 (PP1), a serine/threonine protein phosphatase, controls diverse key cellular events. PP1 catalytic subunits form complexes with a variety of interacting proteins that control its ability to dephosphorylate substrates. Here we show that the human mitotic kinesin-8, KIF18A, directly interacts with PP1γ through a conserved RVxF motif. Our phylogenetic analyses of the kinesins further uncovered the broad conservation of this interaction potential within the otherwise highly diverse motor-protein superfamily. This suggests an ancestral origin of PP1 recruitment to KIF18A and a strategic role in human mitotic cells.