Myosin-X: a MyTH-FERM myosin at the tips of filopodia

Kerber, Michael L.; Cheney, Richard E.

doi:10.1242/jcs.023549

Cited by 138 publications

(145 citation statements)

References 96 publications

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“…In the present study, we wanted to determine the mechanical and biochemical properties of the dimeric form of the molecule because it seems most likely that this is the functional form of the motor within the filopodium in vivo (26). To do this, we appended a GCN4 leucine zipper motif shortly after the APCC region.…”

Section: Discussionmentioning

confidence: 99%

“…Rotary-shadowed electron micrographs of a truncated myosin-10 genetic construct that encoded the first 953 amino acids (12) showed a minority of dimeric (two-headed) molecules (∼10%), consistent with the notion that myosin-10 has a weak propensity to dimerize at low protein concentration. Although a picture is emerging about how myosin-10 might be regulated and how it may switch between monomeric and dimeric states (26), little is known about its mechanical properties or how it generates force and movement. To study the mechano-chemistry of dimeric myosin-10, we generated a recombinant protein with a leucine zipper motif appended after amino acid residue 936 to augment dimerization.…”

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confidence: 99%

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Myosin-10 produces its power-stroke in two phases and moves processively along a single actin filament under low load

Takagi

Farrow

Billington

et al. 2014

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

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Myosin-10 is an actin-based molecular motor that participates in essential intracellular processes such as filopodia formation/ extension, phagocytosis, cell migration, and mitotic spindle maintenance. To study this motor protein's mechano-chemical properties, we used a recombinant, truncated form of myosin-10 consisting of the first 936 amino acids, followed by a GCN4 leucine zipper motif, to force dimerization. Negative-stain electron microscopy reveals that the majority of molecules are dimeric with a head-to-head contour distance of ∼50 nm. In vitro motility assays show that myosin-10 moves actin filaments smoothly with a velocity of ∼310 nm/s. Steady-state and transient kinetic analysis of the ATPase cycle shows that the ADP release rate (∼13 s −1 ) is similar to the maximum ATPase activity (∼12-14 s −1 ) and therefore contributes to rate limitation of the enzymatic cycle. Single molecule optical tweezers experiments show that under intermediate load (∼0.5 pN), myosin-10 interacts intermittently with actin and produces a power stroke of ∼17 nm, composed of an initial 15-nm and subsequent 2-nm movement. At low optical trap loads, we observed staircaselike processive movements of myosin-10 interacting with the actin filament, consisting of up to six ∼35-nm steps per binding interaction. We discuss the implications of this load-dependent processivity of myosin-10 as a filopodial transport motor.actomyosin | stable single alpha-helix | optical trapping | myosin X | myosin-5a

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Myosin-10 produces its power-stroke in two phases and moves processively along a single actin filament under low load

Takagi

Farrow

Billington

et al. 2014

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

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“…Indeed, a recent study showed that Hdl-Myo10 inhibited FLMyo10-mediated axonal outgrowth in cortical neurons (Raines et al, 2012). Nevertheless, it is conceivable that this protein has biological functions, which are independent of FL-Myo10, such as serving as a scaffolding protein, since Hdl-Myo10 has multiple regions that are important for interacting with proteins and lipids (Kerber and Cheney, 2011).…”

Section: Introductionmentioning

confidence: 99%

Myosin X and its motorless isoform differentially modulate dendritic spine development by regulating trafficking and retention of vasodilator-stimulated phosphoprotein

Lin

Hurley

Raines

et al. 2013

Journal of Cell Science

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SummaryMyosin X (Myo10) is an unconventional myosin with two known isoforms: full-length (FL)-Myo10 that has motor activity, and a recently identified brain-expressed isoform, headless (Hdl)-Myo10, which lacks most of the motor domain. FL-Myo10 is involved in the regulation of filopodia formation in non-neuronal cells; however, the biological function of Hdl-Myo10 remains largely unknown. Here, we show that FL-and Hdl-Myo10 have important, but distinct, roles in the development of dendritic spines and synapses in hippocampal neurons. FL-Myo10 induces formation of dendritic filopodia and modulates filopodia dynamics by trafficking the actin-binding protein vasodilator-stimulated phosphoprotein (VASP) to the tips of filopodia. By contrast, Hdl-Myo10 acts on dendritic spines to enhance spine and synaptic density as well as spine head expansion by increasing the retention of VASP in spines. Thus, this study demonstrates a novel biological function for Hdl-Myo10 and an important new role for both Myo10 isoforms in the development of dendritic spines and synapses.

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“…Recent studies suggest that both the Arp2/3 complex and formins could collaborate in filopodia initiation (Block et al, 2012;Breitsprecher et al, 2012). In addition, several proteins including IRSp53 (Ahmed et al, 2010) and Myosin X (Kerber and Cheney, 2011) have been shown to contribute to filopodia formation suggesting that multiple mechanisms of filopodia formation might exist in different cell types. In Dictyostelium, filopodia form mainly by actin tip nucleation since the Arp2/3 complex is dispensable for their formation (Steffen et al, 2006) and the Diaphanous related formin, dDia2 is required for their extension (Schirenbeck et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Dictyostelium ACAP-A is an ArfGAP involved in cytokinesis, cell migration and actin cytoskeleton dynamics

Dias¹,

Blanc²,

Thazar-Poulot

et al. 2012

Journal of Cell Science

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ACAPs and ASAPs are Arf-GTPase-activating proteins with BAR, PH, GAP and ankyrin repeat domains and are known to regulate vesicular traffic and actin cytoskeleton dynamics in mammalian cells. The amoeba Dictyostelium has only two proteins with this domain organization, instead of the six in human, enabling a more precise functional analysis. Genetic invalidation of acapA resulted in multinucleated cells with cytokinesis defects. Mutant acapA(-) cells were hardly motile and their multicellular development was significantly delayed. In addition, formation of filopodial protrusions was deficient in these cells. Conversely, re-expression of ACAP-A-GFP resulted in numerous and long filopodia-like protrusions. Mutagenesis studies showed that the ACAP-A actin remodeling function was dependent on its ability to activate its substrate, the small GTPase ArfA. Likewise, the expression of a constitutively active ArfA•GTP mutant in wild-type cells led to a significant reduction in filopodia length. Together, our data support a role for ACAP-A in the control of the actin cytoskeleton organization and dynamics through an ArfA-dependent mechanism

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Myosin-X: a MyTH-FERM myosin at the tips of filopodia

Cited by 138 publications

References 96 publications

Myosin-10 produces its power-stroke in two phases and moves processively along a single actin filament under low load

Myosin-10 produces its power-stroke in two phases and moves processively along a single actin filament under low load

Myosin X and its motorless isoform differentially modulate dendritic spine development by regulating trafficking and retention of vasodilator-stimulated phosphoprotein

Dictyostelium ACAP-A is an ArfGAP involved in cytokinesis, cell migration and actin cytoskeleton dynamics

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