Determinant factors for residence time of kinesin motors at microtubule ends

Abstract

Kinesins constitute a superfamily of microtubule (MT)-based motor proteins, which can perform diverse biological functions in cells such as transporting vesicle, regulating MT dynamics, and segregating chromosome. Some motors such as kinesin-1, kinesin-2, and kinesin-3 do the activity mainly on the MT lattice, while others such as kinesin-7 and kinesin-8 do the activity mainly at the MT plus end. To perform the different functions, it is required that the former motors can reside on the MT lattice for longer times than at the end, while the latter motors can reside at the MT plus end for long times. Here, a simple but general theory of the MT-end residence time of the kinesin motor is presented, with which the factors dictating the residence time are determined. The theory is further used to study specifically the MT-end residence times of Drosophila kinesin-1, kinesin-2/KIF3AB, kinesin-3/Unc104, kinesin-5/Eg5, kinesin-7/CENP-E, and kinesin-8/Kip3 motors, with the theoretical results being in agreement with the available experimental data.

Keywords: Detachment time; Kinesin; Microtubule end; Molecular motor.

Fig. 1

The mechanochemical coupling pathway of the kinesin motor on the MT lattice. a–f The state transitions following ATP hydrolysis and Pi release in the rear head (see Section 2.1 for detailed descriptions). For clarity, the state transitions following ATP hydrolysis and Pi release in the front head are not shown, and ATP hydrolysis and Pi release are simply described as one step of ATP transition to ADP. The thickness of an arrow represents the relative magnitude of the probability of the transition between the two states connected by the arrow under no load on the motor

Fig. 2

The mechanochemical coupling pathway of the kinesin motor at the MT plus end. a–e The state transitions following ATP hydrolysis and Pi release in the rear head (see Section 2.2 for detailed descriptions). For clarity, the state transitions following ATP hydrolysis and Pi release in the front head are not shown. Note that the pathway at the MT end is the same as that on the MT lattice except that in the former, the motor cannot take the forward step because no front tubulin is present

Fig. 3

Effects of k⁽⁺⁾ and E₀ on MT-end residence time T_r. ${\epsilon }_0$ = 0.1 ${\text{s}}^{-1}$. a T_r versus k⁽⁺⁾ for different values of E₀. b T_r versus E₀ for different values of k.⁽⁺⁾

Fig. 4

Effect of ${\epsilon }_0$ on MT-end residence time T_r. T_r versus k⁽⁺⁾ for two values of ${\epsilon }_0$ and different values of E₀. a E₀ = 0. b E₀ = 1k_BT. c E₀ = 2k_BT. d E₀ = 3k_BT. e E₀ = 4k_BT. f E₀ = 5k_BT

Fig. 5

Load dependence of the velocity of the kinesin motor moving processively on the MT lattice. Lines are theoretical results, and dots are experimental data. a Results for Drosophila kinesin-1. The experimental data are taken from Andreasson et al. [33]. b Results for mammalian kinesin-2/KIF3AB. The experimental data are taken from Andreasson et al. [36]. c Results for C. elegans kinesin-3/Unc104 dimer. The experimental data are taken from Tomishige et al. [37]. d Results for kinesin-5/Eg5. The experimental data are taken from Valentine et al. [41]. e Results for full-length kinesin-7/CENP-E. The experimental data are taken from Gudimchuk et al. [42]. f Results for yeast kinesin-8/Kip3. The experimental data for the velocity without the inclusion of the slip are taken from Jannasch et al. [43]

Fig. 6

MT-end residence times for different families of kinesin motors. K1, K2, K3, K5, K7, and K8 represent Drosophila kinesin-1, mammalian kinesin-2/KIF3AB, Caenorhabditis elegans kinesin-3/Unc104, kinesin-5/Eg5, full-length kinesin-7/CENP-E, and yeast kinesin-8/Kip3 motors, respectively. The theoretical values (gray columns) are calculated with parameter values given in Table 1. The experimental values (red columns) for K1, K5, K7, and K8 are taken from Gudimchuk et al. [35], from Chen and Hancock [15], from Gudimchuk et al. [35], and from Varga et al. [18], respectively. To see the effect of ${\epsilon }_0$ on the MT-end residence times, the theoretical values calculated with ${\epsilon }_0$ = 0 are also shown (indicated by the asterisk (*)

Fig. 7

Results of the velocity on the MT lattice (a) and the residence times at the MT end (b) for WT, G262K, N263E, S266R, Triple, and S266A rat kinesin-1 motors. The theoretical values (gray columns) are calculated with parameter values given in Table 2. The experimental values (red columns) are taken from Belsham and Friel [44]