Kinesin-8 molecular motors: putting the brakes on chromosome oscillations.
ABSTRACT Recent studies suggest that the human Kinesin-8 molecular motor Kif18A has a role in chromosome congression. Specifically, these studies find that Kif18A promotes chromosome congression by attenuating chromosome oscillation magnitudes. Together with recent modeling work, in vitro studies, and the analysis of in vivo yeast data, these reports reveal how Kinesin-8 molecular motors might control chromosome oscillation amplitudes by spatially regulating the dynamic instability of microtubule plus-ends within the mitotic spindle.
Full-textDOI: · Available from: Kerry Bloom, May 28, 2015
SourceAvailable from: conservancy.umn.edu
[Show abstract] [Hide abstract]
ABSTRACT: This paper presents a new multiscale molecular dynamic model for investigating the effects of external interactions, such as contact and impact, during stepping and docking of motor proteins and other biomolecular systems. The model retains the mass properties ensuring that the result satisfies Newton’s second law. This idea is presented using a simple particle model to facilitate discussion of the rigid body model; however, the particle model does provide insights into particle dynamics at the nanoscale. The resulting three-dimensional model predicts a significant decrease in the effect of the random forces associated with Brownian motion. This conclusion runs contrary to the widely accepted notion that the motor protein’s movements are primarily the result of thermal effects. This work focuses on the mechanical aspects of protein locomotion; the effect ATP hydrolysis is estimated as internal forces acting on the mechanical model. In addition, the proposed model can be numerically integrated in a reasonable amount of time. Herein, the differences between the motion predicted by the old and new modeling approaches are compared using a simplified model of myosin V.Multibody System Dynamics 04/2015; 33(4). DOI:10.1007/s11044-014-9431-x · 1.75 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Selectively stabilized microtubules (MTs) form in the lamella of fibroblasts and contribute to cell migration. A Rho-mDia-EB1 pathway regulates the formation of stable MTs, yet how selective stabilization of MTs is achieved is unknown. Kinesin activity has been implicated in selective MT stabilization and a number of kinesins regulate MT dynamics both in vitro and in cells. Here, we show that the mammalian homolog of Xenopus XKLP1, Kif4, is both necessary and sufficient for the induction of selective MT stabilization in fibroblasts. Kif4 localized to the ends of stable MTs and participated in the Rho-mDia-EB1 MT stabilization pathway since Kif4 depletion blocked mDia- and EB1-induced selective MT stabilization and EB1 was necessary for Kif4 induction of stable MTs. Kif4 and EB1 interacted in cell extracts, and binding studies revealed that the tail domain of Kif4 interacted directly with the N-terminal domain of EB1. Consistent with its role in regulating formation of stable MTs in interphase cells, Kif4 knockdown inhibited migration of cells into wounded monolayers. These data identify Kif4 as a novel factor in the Rho-mDia-EB1 MT stabilization pathway and cell migration.PLoS ONE 03/2014; 9(3):e91568. DOI:10.1371/journal.pone.0091568 · 3.53 Impact Factor