Casein kinase 2 reverses tail-independent inactivation of kinesin-1

Xu, Jing; Reddy, Babu J.N.; Anand, Preetha; Shu, Zhang; Cermelli, Silvia; Mattson, Michelle K.; Tripathy, Suvranta K.; Hoss, Matthew T.; James, N.; King, Stephen J.; Huang, Lan; Bardwell, Lee; Gross, Steven P.

doi:10.1038/ncomms1760

Cited by 33 publications

(42 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One rationalization of these two observations is that, although kinesin inactivation/reactivation does not depend directly on kinesin's nucleotide state, CK2 causes a conformational change that both activates the motor and causes ADP release. We previously ruled out gross conformational changes: Inactivation occurs at the level of the single head, and no large change was observed in the sedimentation characteristics of the protein (13). Instead, we hypothesize that a smaller change occurs.…”

Section: Inactive Kinesin Undergoes a Conformational Change Resulting Inmentioning

confidence: 95%

“…Previously, we reported that when stored ("aged") on ice, kinesin went inactive over the course of a few hours and lost the ability to bind to microtubules (13). New experiments have confirmed such inactivation and have found that it is accelerated at higher temperatures as measured by both microtubule pelleting assays of dimers (Fig.…”

Section: Kinesin-1 Inactivation Is Accelerated At Physiologic Temperamentioning

confidence: 82%

“…3A). This result cannot be explained by the CK2 ATPase activity (because that was minimal-0.003 s ) or by CK2's phosphorylation of kinesin, because the same 35% increase in kinesin's ATPase activity was observed even in the presence of tetrabromocinnamic acid (TBCA), a drug that inhibits CK2 enzymatic activity (13,15). Thus, in the absence of microtubules, CK2 appears to accelerate kinesin's ADP release.…”

Section: Kinesin-1 Inactivation Is Accelerated At Physiologic Temperamentioning

confidence: 99%

“…3B). CK2α was used rather than holoenzyme, because in contrast to kinesin-CK2, the kinesin-CK2α interaction is transient (13), so CK2α and kinesin run separately in the native gels.…”

Section: Kinesin-1 Inactivation Is Accelerated At Physiologic Temperamentioning

confidence: 99%

“…One such kinase is casein kinase 2 (CK2), which is involved in development (10), is up-regulated in various cancers (11), and is decreased in neurodegeneration (12). We found that, over time, kinesin loses its ability to bind microtubules (becomes "inactive") and that this loss of activity could be reversed by CK2 (13).…”

mentioning

confidence: 99%

See 4 more Smart Citations

CK2 activates kinesin via induction of a conformational change

Mattson-Hoss¹,

Niitani²,

Gordon³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Kinesin is the canonical plus-end microtubule motor and has been the focus of intense study since its discovery in 1985. We previously demonstrated a time-dependent inactivation of kinesin in vitro that was fully reversible by the addition of purified casein kinase 2 (CK2) and showed that this inactivation/reactivation pathway was relevant in cells. Here we show that kinesin inactivation results from a conformational change that causes the neck linker to be positioned closer to the motor domain. Furthermore, we show that treatment of kinesin with CK2 prevents and reverses this repositioning. Finally, we demonstrate that CK2 treatment facilitates ADP dissociation from the motor, resulting in a nucleotidefree state that promotes microtubule binding. Thus, we propose that kinesin inactivation results from neck-linker repositioning and that CK2-mediated reactivation results from CK2's dual ability to reverse this repositioning and to promote ADP release.cargo travel | multiple-motor transport | transport regulation

show abstract

Section: Inactive Kinesin Undergoes a Conformational Change Resulting Inmentioning

confidence: 95%

Section: Kinesin-1 Inactivation Is Accelerated At Physiologic Temperamentioning

confidence: 82%

Section: Kinesin-1 Inactivation Is Accelerated At Physiologic Temperamentioning

confidence: 99%

“…3B). CK2α was used rather than holoenzyme, because in contrast to kinesin-CK2, the kinesin-CK2α interaction is transient (13), so CK2α and kinesin run separately in the native gels.…”

Section: Kinesin-1 Inactivation Is Accelerated At Physiologic Temperamentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

CK2 activates kinesin via induction of a conformational change

Mattson-Hoss¹,

Niitani²,

Gordon³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

Native kinesin‐1 does not bind preferentially to GTP‐tubulin‐rich microtubules in vitro

King

2017

Cytoskeleton

Self Cite

View full text Add to dashboard Cite

Molecular motors such as kinesin-1 work in small teams to actively shuttle cargos in cells, for example in polarized transport in axons. Here we examined the potential regulatory role of the nucleotide state of tubulin on the run length of cargos carried by multiple kinesin motors, using an optical trapping-based in vitro assay. Based on a previous report that kinesin binds preferentially to GTP-tubulin-rich microtubules, we anticipated that multiple-kinesin cargos would run substantially greater distances along GMPCPP microtubules than along GDP microtubules. Surprisingly, we did not uncover any significant differences in run length between microtubule types. A combination of single-molecule experiments, comparison with previous theory, and classic microtubule affinity pulldown assays revealed that native kinesin-1 does not bind preferentially to GTP-tubulin-rich microtubules. The apparent discrepancy between our observations and the previous report likely reflects differences in post-translational modifications between the native motors used here and the recombinant motors examined previously. Future investigations will help shed light on the interplay between the motor’s post-translational modification and the microtubule’s nucleotide-binding state for transport regulation in vivo.

show abstract

The Contribution of the C-Terminal Tails of Microtubules in Altering the Force Production Specifications of Multiple Kinesin-1

Feizabadi

2016

Cell Biochem Biophys

View full text Add to dashboard Cite

The extent to which beta tubulin isotypes contribute to the function of microtubules and the microtubule-driven transport of molecular motors is poorly understood. The major differences in these isotypes are associated with the structure of their C-terminal tails. Recent studies have revealed a few aspects of the C-terminal tails' regulatory role on the activities of some of the motor proteins on a single-molecule level. However, little attention is given to the degree to which the function of a team of motor proteins can be altered by the microtubule's tail. In a set of parallel experiments, we investigated this open question by studying the force production of several kinesin-1 (kinesin) molecular motors along two groups of microtubules: regular ones and those microtubules whose C-terminals are cleaved by subtilisin digestion. The results indicate that the difference between the average of the force production of motors along two types of microtubules is statistically significant. The underlying mechanism of such production is substantially different as well. As compared to untreated microtubules, the magnitude of the binding time of several kinesin-1 is almost three times greater along subtilisin-treated microtubules. Also, the velocity of the group of kinesin molecules shows a higher sensitivity to external loads and reduces significantly under higher loads along subtilisin-treated microtubules. Together, this work shows the capacity of the tails in fine-tuning the force production characteristics of several kinesin molecules.

show abstract

Casein kinase 2 reverses tail-independent inactivation of kinesin-1

Cited by 33 publications

References 44 publications

CK2 activates kinesin via induction of a conformational change

CK2 activates kinesin via induction of a conformational change

Native kinesin‐1 does not bind preferentially to GTP‐tubulin‐rich microtubules in vitro

The Contribution of the C-Terminal Tails of Microtubules in Altering the Force Production Specifications of Multiple Kinesin-1

Contact Info

Product

Resources

About