Coupling of Two Non-processive Myosin 5c Dimers Enables Processive Stepping along Actin Filaments

Gunther, Laura K.; Furuta, Ken’ya; Bao, Jianjun; Urbanowski, Monica K.; Kojima, Hiroaki; White, Howard D.; Sakamoto, Takeshi

doi:10.1038/srep04907

Cited by 16 publications

(28 citation statements)

References 57 publications

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“…Consistent with previous studies [1–3], MyoVc did not move processively on individual actin filaments at 1 mM MgATP (Figure 1B). Occasionally, Qdots associated with individual actin filaments for 1.0 ± 1.4 seconds (mean ± SD), but gave no net displacement (Table 1 and Movie S1).…”

Section: Resultssupporting

confidence: 92%

“…remains tightly bound to actin for more than half of its ATPase cycle. Transient kinetic studies of a single-headed MyoVc inferred a duty cycle <50%, implying that the kinetics of the MyoVc motor domain are incompatible with processivity [1–3]. …”

Section: Resultsmentioning

confidence: 99%

“…Thus it was surprising when kinetic and single molecule assays showed that human Myosin Vc (MyoVc) was not processive on single actin filaments [1–3]. We explored the possibility that MyoVc is processive only under conditions that resemble its biological context.…”

mentioning

confidence: 99%

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Myosin Vc Is Specialized for Transport on a Secretory Superhighway

2016

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Summary A hallmark of the well-studied vertebrate class Va myosin is its ability to take multiple steps on actin as a single molecule without dissociating, a feature called “processivity”. Thus it was surprising when kinetic and single molecule assays showed that human Myosin Vc (MyoVc) was not processive on single actin filaments [1–3]. We explored the possibility that MyoVc is processive only under conditions that resemble its biological context. Recently, it was shown that zymogen vesicles are transported on actin “superhighways” composed of parallel actin cables nucleated by formins from the plasma membrane [4]. Loss of these cables compromises orderly apical targeting of vesicles. MyoVc has been implicated in transporting secretory vesicles to the apical membrane [5]. We hypothesized that actin cables regulate the processive properties of MyoVc. We show that MyoVc is unique in taking variable size steps, which are frequently in the backward direction. Results obtained with chimeric constructs implicate the lever arm/rod of MyoVc as being responsible for these properties. Actin bundles allow single MyoVc motors to move processively. Remarkably, even teams of MyoVc motors require actin bundles to move continuously at physiological ionic strength. The irregular stepping pattern of MyoVc, which may result from flexibility in the lever arm/rod of MyoVc, appears to be a unique structural adaptation that allows the actin track to spatially restrict the activity of MyoVc to specialized actin cables in order to co-ordinate and target the final stages of vesicle secretion.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

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Myosin Vc Is Specialized for Transport on a Secretory Superhighway

2016

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“…In several experiments, the interaction of two coupled kinesins has been addressed [22], also under external load forces [24]. Other experiments using DNA scaffolds have studied assemblies of two myosin V motors [25], two nonprocessive myosin Vc [26], several processive and nonprocessive kinesin motors [27], and a tug-of-war between dynein and kinesin motors [23].…”

Section: Introductionmentioning

confidence: 99%

External forces influence the elastic coupling effects during cargo transport by molecular motors

et al. 2015

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Cellular transport is achieved by the cooperative action of molecular motors which are elastically linked to a common cargo. When the motors pull on the cargo at the same time, they experience fluctuating elastic strain forces induced by the stepping of the other motors. These elastic coupling forces can influence the motors' stepping and unbinding behavior and thereby the ability to transport cargos. Based on a generic single motor description, we introduce a framework that explains the response of two identical molecular motors to a constant external force. In particular, we relate the single motor parameters, the coupling strength and the external load force to the dynamics of the motor pair. We derive four distinct transport regimes and determine how the crossover lines between the regimes depend on the load force. Our description of the overall cargo dynamics takes into account relaxational displacements of the cargo caused by the unbinding of one motor. For large forces and weak elastic coupling these back-shifts dominate the displacements. To develop an intuitive understanding about motor cooperativity during cargo transport, we introduce a time scale for load sharing. This time scale allows us to predict how the regulation of single motor parameters influences the cooperativity. As an example, we show that up-regulating the single motor processivity enhances load sharing of the motor pair.

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“…Unlike Myo5a and Myo5b, Myo5c is a non-processive motor (30,31). Recently, it was shown that two dimers of Myo5c molecules on a DNA scaffold enabled processive steps along actin filaments (32). Although the GTD of Myo5c has a similar overall structure as Myo5a and Myo5b (14 -17), it is still an open question whether Myo5c is regulated by a tail inhibition mechanism.…”

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confidence: 99%

Identification of the Isoform-specific Interactions between the Tail and the Head of Class V Myosin

Yao

Shen

et al. 2016

Journal of Biological Chemistry

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Vertebrates have three isoforms of class V myosin (Myo5), Myo5a, Myo5b, and Myo5c, which are involved in transport of multiple cargoes. It is well established that the motor functions of Myo5a and Myo5b are regulated by a tail inhibition mechanism. Here we found that the motor function of Myo5c was also inhibited by its globular tail domain (GTD), and this inhibition was abolished by high Ca 2؉ , indicating that the tail inhibition mechanism is conserved in vertebrate Myo5. Interestingly, we found that Myo5a-GTD and Myo5c-GTD were not interchangeable in terms of inhibition of motor function, indicating isoform-specific interactions between the GTD and the head of Myo5. To identify the isoform-specific interactions, we produced a number of Myo5 chimeras by swapping the corresponding regions of Myo5a and Myo5c. We found that Myo5a-GTD, with its H11-H12 loop being substituted with that of Myo5c, was able to inhibit the ATPase activity of Myo5c and that Myo5a-GTD was able to inhibit the ATPase activity of Myo5c-S1 and Myo5c-HMM only when their IQ1 motif was substituted with that of Myo5a. Those results indicate that the H11-H12 loop in the GTD and the IQ1 motif in the head dictate the isoformspecific interactions between the GTD and head of Myo5. Because the IQ1 motif is wrapped by calmodulin, whose conformation is influenced by the sequence of the IQ1 motif, we proposed that the calmodulin bound to the IQ1 motif interacts with the H11-H12 loop of the GTD in the inhibited state of Myo5.

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Coupling of Two Non-processive Myosin 5c Dimers Enables Processive Stepping along Actin Filaments

Cited by 16 publications

References 57 publications

Myosin Vc Is Specialized for Transport on a Secretory Superhighway

Myosin Vc Is Specialized for Transport on a Secretory Superhighway

External forces influence the elastic coupling effects during cargo transport by molecular motors

Identification of the Isoform-specific Interactions between the Tail and the Head of Class V Myosin

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