Shaking the myosin family tree: Biochemical kinetics defines four types of myosin motor

Bloemink, Marieke J.; Geeves, Michael A.

doi:10.1016/j.semcdb.2011.09.015

Cited by 109 publications

(120 citation statements)

References 65 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…S3). The ratio of affinities (K 10 ∕K 6 ¼ K DA ∕K A ) has been termed the coupling constant (22,23), and the calculated value of 5.5 is similar to previously published values for myo1b (28,29); however, it is larger than a previously reported value for myo1c (10). Based on the solution kinetics, ADP release is expected to be rate limiting for actomyosin detachment at saturating ATP concentrations; however, a slower transition (likely associated with phosphate release) (16,19) limits the rate of the overall ATPase cycle.…”

Section: Resultsmentioning

confidence: 99%

“…A coupling constant of <10 is viewed as a signature for a tension sensor (22,23), and myo1c 3IQ has a coupling constant of 5.5, placing it in the tension-sensor class. Myo1c 3IQ (10) and myo1b (28,29) have similar coupling constants and kinetic rate constants, and thus one would expect them to have similar mechanics and functions; however, this is clearly not the case (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the rate of actin translocation in the in vitro motility assay is similar for both myo1b (21) and myo1c (16) (when corrected for the differences in length of the light chain-binding domain). Given the similarity of their unloaded biochemical properties, one may have expected myo1c to share the force-sensing properties of myo1b (22,23).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Myosin IC generates power over a range of loads via a new tension-sensing mechanism

Greenberg

Lin

Goldman

et al. 2012

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

132

View full text Add to dashboard Cite

Myosin IC (myo1c), a widely expressed motor protein that links the actin cytoskeleton to cell membranes, has been associated with numerous cellular processes, including insulin-stimulated transport of GLUT4, mechanosensation in sensory hair cells, endocytosis, transcription of DNA in the nucleus, exocytosis, and membrane trafficking. The molecular role of myo1c in these processes has not been defined, so to better understand myo1c function, we utilized ensemble kinetic and single-molecule techniques to probe myo1c's biochemical and mechanical properties. Utilizing a myo1c construct containing the motor and regulatory domains, we found the force dependence of the actin-attachment lifetime to have two distinct regimes: a force-independent regime at forces <1 pN, and a highly force-dependent regime at higher loads. In this force-dependent regime, forces that resist the working stroke increase the actinattachment lifetime. Unexpectedly, the primary force-sensitive transition is the isomerization that follows ATP binding, not ADP release as in other slow myosins. This force-sensing behavior is unique amongst characterized myosins and clearly demonstrates mechanochemical diversity within the myosin family. Based on these results, we propose that myo1c functions as a slow transporter rather than a tension-sensitive anchor.is a widely expressed myosin-I isoform that has been associated with several important cellular processes, including endocytosis (1), exocytosis (2) (including insulin-stimulated GLUT4 translocation to the cell membrane; refs. 3-5), membrane ruffling (6), transcription of DNA in the nucleus (7,8), and mechanosensing in sensory hair cells (9-13). Although it is known that myo1c links cell membranes to the actin cytoskeleton (14, 15), its molecular role in these cellular processes has not been determined. For example, in its proposed role in exocytosis, it is not known if myo1c acts as a motor for transport, moving vesicles into position for plasma membrane fusion and/or as a tension-sensitive anchor that docks exocytic vesicles to the actin cytoskeleton and plasma membrane.Most members of the myosin family share the same kinetic pathway for ATP hydrolysis, in which force-generating structural changes are linked to release of inorganic phosphate and ADP, but different myosin isoforms have evolved different biochemical reaction rates and force-dependent kinetics to suit their cellular functions. For example, in myosins that are thought to act as tension-sensitive anchors, the kinetic steps that limit actomyosin detachment are highly sensitive to load. In contrast, myosins that are thought to act as transporters have actin-detachment kinetics that are less sensitive to load, allowing work to be performed over a range of forces. Thus, insight into the molecular role of myosin in the cell can be gained from evaluating the kinetic and mechanical properties of the motor.Previous biochemical analyses have shown that myo1c is a lowduty ratio motor (i.e., it spends most of its biochemical cycle detached from act...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Myosin IC generates power over a range of loads via a new tension-sensing mechanism

Greenberg

Lin

Goldman

et al. 2012

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

132

View full text Add to dashboard Cite

show abstract

“…We recently proposed that the mechanical/motor activity of myosin motors can be classified into four types: fast, powerful movers; slow, efficient force holders; sensors; and processive/signal transducers (Bloemink and Geeves, 2011). In addition to changes in duty ratio across the series, one of the distinguishing features of different types of motor activity is how the ADP release step is used in different ways.…”

Section: The Central Role Of Adp In Mechanical Activitymentioning

confidence: 99%

Myosin isoforms and the mechanochemical cross-bridge cycle

Walklate

Ujfalusi

Geeves

2016

Journal of Experimental Biology

Self Cite

View full text Add to dashboard Cite

At the latest count the myosin family includes 35 distinct groups, all of which have the conserved myosin motor domain attached to a neck or lever arm, followed by a highly variable tail or cargo binding region. The motor domain has an ATPase activity that is activated by the presence of actin. One feature of the myosin ATPase cycle is that it involves an association/dissociation with actin for each ATP hydrolysed. The cycle has been described in detail for a large number of myosins from different classes. In each case the cycle is similar, but the balance between the different molecular events in the cycle has been altered to produce a range of very different mechanical activities. Myosin may spend most of the ATPase cycle attached to actin (high duty ratio), as in the processive myosin (e.g. myosin V) or the strain-sensing myosins (e.g. myosin 1c). In contrast, most muscle myosins spend 80% of their ATPase cycle detached from actin. Within the myosin IIs found in human muscle, there are 11 different sarcomeric myosin isoforms, two smooth muscle isoforms as well as three non-muscle isoforms. We have been exploring how the different myosin isoforms have adapted the cross-bridge cycle to generate different types of mechanical activity and how this goes wrong in inherited myopathies. The ideas are outlined here.

show abstract

“…The conventional myosins, which comprise the non-muscle myosin II family and the skeletal, cardiac and smooth muscle myosins, assemble to form bipolar filaments that mediate sliding and crosslinking of actin filaments to generate contractility and tension. By contrast, unconventional myosins do not form filaments but, rather, function as either monomeric or dimeric cargo transporters, regulators of actin organisation, adjustable tethers for organelles, and/or as loaddependent tension sensors (Bloemink and Geeves, 2011;Hartman et al, 2011). The precise cellular roles of the different classes of unconventional myosins are mainly due to their divergent cargobinding tail regions that mediate distinct interactions for targeting to various subcellular locations.…”

Section: Introductionmentioning

confidence: 99%

Myosin VI and its cargo adaptors – linking endocytosis and autophagy

Tumbarello

Kendrick‐Jones

Buß

2013

Journal of Cell Science

117

127

View full text Add to dashboard Cite

SummaryThe coordinated trafficking and tethering of membrane cargo within cells relies on the function of distinct cytoskeletal motors that are targeted to specific subcellular compartments through interactions with protein adaptors and phospholipids. The unique actin motor myosin VI functions at distinct steps during clathrin-mediated endocytosis and the early endocytic pathway -both of which are involved in cargo trafficking and sorting -through interactions with Dab2, GIPC, Tom1 and LMTK2. This multifunctional ability of myosin VI can be attributed to its cargo-binding tail region that contains two protein-protein interaction interfaces, a ubiquitin-binding motif and a phospholipid binding domain. In addition, myosin VI has been shown to be a regulator of the autophagy pathway, because of its ability to link the endocytic and autophagic pathways through interactions with the ESCRT-0 protein Tom1 and the autophagy adaptor proteins T6BP, NDP52 and optineurin. This function has been attributed to facilitating autophagosome maturation and subsequent fusion with the lysosome. Therefore, in this Commentary, we discuss the relationship between myosin VI and the different myosin VI adaptor proteins, particularly with regards to the spatial and temporal regulation that is required for the sorting of cargo at the early endosome, and their impact on autophagy.

show abstract

Shaking the myosin family tree: Biochemical kinetics defines four types of myosin motor

Cited by 109 publications

References 65 publications

Myosin IC generates power over a range of loads via a new tension-sensing mechanism

Myosin IC generates power over a range of loads via a new tension-sensing mechanism

Myosin isoforms and the mechanochemical cross-bridge cycle

Myosin VI and its cargo adaptors – linking endocytosis and autophagy

Contact Info

Product

Resources

About