Functional Characterization of Human Myosin-18A and Its Interaction with F-actin and GOLPH3

Taft, Manuel H.; Behrmann, Elmar; Munske-Weidemann, Lena-Christin; Thiel, Claudia; Raunser, Stefan; Manstein, Dietmar J.

doi:10.1074/jbc.m113.497180

Cited by 58 publications

(85 citation statements)

References 46 publications

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“…Specifically, both possess a C-terminal PDZ domain-binding motif, and M18Aa also contains an N-terminal extension containing a KE-rich domain, an ATP-insensitive actin-binding site, and a PDZ domain. Unlike NM2, its closest relative, M18A has no motor activity [1][2][3]. Despite this, we asked whether M18A polymerizes into bipolar filaments like NM2.…”

Section: Resultsmentioning

confidence: 99%

“…These sites, which include a PDZ domain, PDZ domain ligand, and potential SH3 domain ligands, could recruit specific molecules to filaments ( Figure 4B). M18A has been shown to interact with the Rac GEF b-PIX in a complex with PAK2 and GIT1 [14,18], with a complex containing LRAP35A and the NM2 kinase MRCK [15], and with the Golgiresident protein GOLPH3 [2,19]. M18A could also link hybrid filaments to firmly anchored structures against which hybrid filaments could generate force even when actin filaments are not present on both sides of the bipolar myosin filament (Figure 4C).…”

Section: Discussionmentioning

confidence: 99%

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Myosin 18A Coassembles with Nonmuscle Myosin 2 to Form Mixed Bipolar Filaments

et al. 2015

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Nonmusclemyosin 2 (NM-2) powers cell motility and tissue morphogenesis by assembling into bipolar filaments that interact with actin. Although the enzymatic properties of purified NM-2 motor fragments have been determined, the emergent properties of filament ensembles are unknown. Using single myosin filament in vitro motility assays, we report fundamental differences in filaments formed of different NM-2 motors. Filaments consisting of NM2-B moved processively along actin, while under identical conditions, NM2-A filaments did not. By more closely mimicking the physiological milieu, either by increasing solution viscosity or by co-polymerization with NM2-B, NM2-A containing filaments moved processively. Our data demonstrate that both the kinetic and mechanical properties of these two myosins, in addition to the stochiometry of NM-2 subunits, can tune filament mechanical output. We propose altering NM-2 filament composition is a general cellular strategy for tailoring force production of filaments to specific functions, such as maintaining tension or remodeling actin.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Myosin 18A Coassembles with Nonmuscle Myosin 2 to Form Mixed Bipolar Filaments

et al. 2015

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“…M18Aα differs from M18Aβ in that it contains a 332-residue Nterminal extension that harbors the PDZ domain thought to be responsible for binding GOLPH3 (Taft et al 2013) (Fig. 1, Panel A).…”

Section: M18aα Remains Inactive In the Presence Of Golph3mentioning

confidence: 99%

Re‐evaluating the roles of myosin 18Aα and F‐actin in determining Golgi morphology

et al. 2017

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The peri-centrosomal localization and morphology of the Golgi apparatus depends largely on the microtubule cytoskeleton and the microtubule motor protein dynein. Recent studies proposed that myosin 18Aα (M18Aα) also contributes to Golgi morphology by binding the Golgi protein GOLPH3 and walking along adjacent actin filaments to stretch the Golgi into its classic ribbon structure. Biochemical analyses have shown, however, that M18A is not an actin-activated ATPase and lacks motor activity. Our goal, therefore, was to define the precise molecular mechanism by which M18Aα determines Golgi morphology. We show that purified M18Aα remains inactive in the presence of GOLPH3, arguing against the Golgi-specific activation of the myosin. Using M18A-specific antibodies and expression of GFP-tagged M18Aα, we find no evidence that it localizes to the Golgi. Moreover, several cell lines with reduced or eliminated M18Aα expression exhibited normal Golgi morphology. Interestingly, actin filament disassembly resulted in a marked reduction in lateral stretching of the Golgi in both control and M18Aα-deficient cells. Importantly, this reduction was accompanied by an expansion of the Golgi in the vertical direction, vertical movement of the centrosome, and increases in the height of both the nucleus and the cell. Collectively, our data indicate that M18Aα does not localize to the Golgi or play a significant role in determining its morphology, and suggest that global F-actin disassembly alters Golgi morphology indirectly by altering cell shape.

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“…A mutation (S2302*) in MYO18B in humans, which truncates the protein and results in near loss of the protein through nonsense mediated decay, causes skeletal muscle myopathy [59]. Unlike most other myosin isoforms, MYO18A does not have an active motor domain, lacking key residues in regions of the molecule important for ATP hydrolysis for example [60][61][62]. From their sequence similarity, it is likely that MYO18B does not have an active motor domain either.…”

Section: Myo9b and Myo18a Modulators Of Nm2 Filament Organisationmentioning

confidence: 99%

How myosin organization of the actin cytoskeleton contributes to the cancer phenotype

Peckham

2016

Biochemical Society Transactions

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The human genome contains 39 genes that encode myosin heavy chains, classified on the basis of their sequence similarity into 12 classes. Most cells express at least 12 different genes, from at least 8 different classes, which are typically composed of several class 1 genes, at least one class 2 gene, and classes 5, 6, 9, 10, 18 and 19. While the different myosin isoforms all have specific and non-overlapping roles in the cell, in combination they all contribute to the organisation of the actin cytoskeleton, and the shape and phenotype of the cell. Over (or under) expression of these different myosin isoforms can have strong effects on actin organisation, cell shape, and contribute to the cancer phenotype as discussed in this review.

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Functional Characterization of Human Myosin-18A and Its Interaction with F-actin and GOLPH3

Cited by 58 publications

References 46 publications

Myosin 18A Coassembles with Nonmuscle Myosin 2 to Form Mixed Bipolar Filaments

Myosin 18A Coassembles with Nonmuscle Myosin 2 to Form Mixed Bipolar Filaments

Re‐evaluating the roles of myosin 18Aα and F‐actin in determining Golgi morphology

How myosin organization of the actin cytoskeleton contributes to the cancer phenotype

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