Actin Age Orchestrates Myosin-5 and Myosin-6 Run Lengths

Zimmermann, Dennis; Santos, Alicja; Kovar, David R.; Rock, Ronald S.

doi:10.1016/j.cub.2015.06.033

Cited by 54 publications

(58 citation statements)

References 37 publications

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“…It was further shown that not only the isoactin but also its age, determined by its nucleotide state, is involved in myosin sorting: The transporter myosin-5a has a longer run length on “young” actin which is the ADP·Pi state, concomitant with the site of actin polymerization at the plus-end at the cell periphery. Myosin-6, a minus-end directed motor takes longer runs on “old” actin in the ADP state, consistent with its movement to the center of the cell [138]. Sorting mechanism of the actin cytoskeleton result in regions that are enriched for actin signatures that either promote or exclude the interaction with a specific myosin class are cell type specific and dependent on cellular needs [139].…”

Section: Actin-linked Regulationmentioning

confidence: 99%

Various Themes of Myosin Regulation

Heissler

Sellers

2016

Journal of Molecular Biology

119

127

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Members of the myosin superfamily are actin-based molecular motors that are indispensable for cellular homeostasis. The vast functional and structural diversity of myosins accounts for the variety and complexity of the underlying allosteric regulatory mechanisms that determine the activation or inhibition of myosin motor activity and enable precise timing and spatial aspects of myosin function at the cellular level. This review focuses on the molecular basis of posttranslational regulation of eukaryotic myosins from different classes across species by allosteric intrinsic and extrinsic effectors. First, we highlight the impact of heavy and light chain phosphorylation. Second, we outline intramolecular regulatory mechanisms such as autoinhibition and subsequent activation. Third, we discuss diverse extramolecular allosteric mechanisms ranging from actin-linked regulatory mechanisms to myosin:cargo interactions. At last, we briefly outline the allosteric regulation of myosins with synthetic compounds.

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Section: Actin-linked Regulationmentioning

confidence: 99%

Various Themes of Myosin Regulation

Heissler

Sellers

2016

Journal of Molecular Biology

119

127

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“…Corrections for finite filament length and photobleaching need to be included, otherwise both interaction time and run length are underestimated (e.g. see Zimmermann et al [26]). Here, the systematic errors can be on the same order as the statistical error and therefore careful consideration of the evaluation method is essential.…”

Section: Discussionmentioning

confidence: 99%

Challenges in estimating the motility parametersn of single processive motor proteins

Ruhnow

Kloss

Diez

2017

Preprint

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Cytoskeletal motor proteins are essential to the function of a wide range of intracellular mechanosystems. The biophysical characterization of their movement along their filamentous tracks is therefore of large importance. Towards this end, single-molecule, in vitro stepping-motility assays are commonly used to determine motor velocity and run length. However, comparing results from such experiments has proved difficult due to influences from variations in the experimental conditions and the data analysis methods. Here, we investigate the movement of fluorescently-labeled, processive, dimeric motor proteins and propose a unified algorithm to correct the measurements for finite filament length as well as photobleaching. Particular emphasis is put on estimating the statistical errors associated with the proposed evaluation method as knowledge of these values is crucial when comparing measurements from different experiments. Testing our approach with simulated and experimental data from GFP-labeled kinesin-1 motors stepping along immobilized microtubules, we show (i) that velocity distributions should be fitted by a t location-scale probability density function rather than by a norm * al distribution, (ii) that the impossibility to measure events shorter than the image acquisition time needs to be accounted for, (iii) that the interaction time and run length of the motors can be estimated independent of the filament length distribution, and (iv) that the dimeric nature of the motors needs to be considered when correcting for photobleaching. Moreover, our analysis reveals that controlling the temperature during the experiments with a precision below 1 K is of importance. We believe, our method will not only improve the evaluation of experimental data, but will also allow for better statistical comparisons between different populations of motor proteins (e.g. with distinct mutations or linked to different cargos) and filaments (e.g. in distinct nucleotide states or with different posttranslational modifications).

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“…Although ATP-actin and ADP-Pi actin filaments have very similar properties, the ADP-actin accumulating at the minus-end of the filament is less rigid and stable. Interestingly, in vitro MYO5 shows increased run lengths on ADP+Pi-rich filaments, whereas MYO6 which prefers 'old' ADP-rich filaments [6]. Recent cryo-EM structures confirm minor conformational changes between nucleotide states of F-actin [84], as well as within the actin-binding interface of the motor domain of nonmuscle myosin class IIc (MYH14) and MYO6 [77,85].…”

Section: Actin Track Compositionmentioning

confidence: 99%

TheMYO6 interactome: selective motor‐cargo complexes for diverse cellular processes

et al. 2019

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Myosins of class VI (MYO6) are unique actin‐based motor proteins that move cargo towards the minus ends of actin filaments. As the sole myosin with this directionality, it is critically important in a number of biological processes. Indeed, loss or overexpression of MYO6 in humans is linked to a variety of pathologies including deafness, cardiomyopathy, neurodegenerative diseases as well as cancer. This myosin interacts with a wide variety of direct binding partners such as for example the selective autophagy receptors optineurin, TAX1BP1 and NDP52 and also Dab2, GIPC, TOM1 and LMTK2, which mediate distinct functions of different MYO6 isoforms along the endocytic pathway. Functional proteomics has recently been used to identify the wider MYO6 interactome including several large functionally distinct multi‐protein complexes, which highlight the importance of this myosin in regulating the actin and septin cytoskeleton. Interestingly, adaptor‐binding not only triggers cargo attachment, but also controls the inactive folded conformation and dimerisation of MYO6. Thus, the C‐terminal tail domain mediates cargo recognition and binding, but is also crucial for modulating motor activity and regulating cytoskeletal track dynamics.

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Actin Age Orchestrates Myosin-5 and Myosin-6 Run Lengths

Cited by 54 publications

References 37 publications

Various Themes of Myosin Regulation

Various Themes of Myosin Regulation

Challenges in estimating the motility parametersn of single processive motor proteins

TheMYO6 interactome: selective motor‐cargo complexes for diverse cellular processes

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