title: Heterodimerization of Kinesin-2 KIF3AB Modulates Entry into the Processive Run.
abstract: Mammalian KIF3AB is an N-terminal processive kinesin-2 that is best known for its roles in intracellular transport. There has been significant interest in KIF3AB to define the key principles that underlie its processivity but also to define the mechanistic basis of its sensitivity to force. In this study, the kinetics for entry into the processive run were quantified. The results show for KIF3AB that the kinetics of microtubule association at 7 μm-1s-1is less than the rates observed for KIF3AA at 13 μm-1s-1or KIF3BB at 11.9 μm-1s-1ADP release after microtubule association for KIF3AB is 33 s-1and is significantly slower than ADP release from homodimeric KIF3AA and KIF3BB, which reach 80-90 s-1To explore the interhead communication implied by the rate differences at these first steps, we compared the kinetics of KIF3AB microtubule association followed by ADP release with the kinetics for mixtures of KIF3AA plus KIF3BB. Surprisingly, the kinetics of KIF3AB are not equivalent to any of the mixtures of KIF3AA + KIF3BB. In fact, the transients for each of the mixtures overlay the transients for KIF3AA and KIF3BB. These results reveal that intermolecular communication within the KIF3AB heterodimer modulates entry into the processive run, and the results suggest that it is the high rate of microtubule association that drives rebinding to the microtubule after force-dependent motor detachment.
authors.affiliation: From the Department of Biological Sciences and the Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180 and.
authors.forename: Clayton D
authors.initials: CD
authors.lastname: Albracht
authors.affiliation: From the Department of Biological Sciences and the Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180 and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Guzik-Lendrum
authors.affiliation: the Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Ivan
authors.initials: I
authors.lastname: Rayment
authors.affiliation: From the Department of Biological Sciences and the Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180 and sgilbert@rpi.edu.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Gilbert
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019281:Dimerization; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism
chemical_list: C490202:Kif3a protein, mouse; C490672:Kif3b protein, mouse; D000244:Adenosine Diphosphate; D016547:Kinesins
keywords: ATPase; cargo transport; cooperativity; cytoskeleton; intraflagellar transport; kinesin; microtubule; neuron; presteady-state kinetics; processivity