A microtubule-binding myosin required for nuclear anchoring and spindle assembly

Weber, K; Sokac, Anna Marie; Berg, Jonathan S.; Cheney, Richard E.; Bement, William M.

doi:10.1038/nature02834

Cited by 235 publications

(277 citation statements)

References 30 publications

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“…The MyTH4/FERM coupling has not been duplicated in Tetrahymena myosins. Although the roles of MyTH4 and FERM are not well understood, recent studies indicate that MyTH4/FERM interacts with microtubules [Weber et al, 2004], and FERM interacts with actin [Lee et al, 2004] and integrins [Zhang et al, 2004]. Therefore, the MyTH4/FERM motif is thought to be a link to the cytoskeleton.…”

Section: Myosin Genes Encode Divergent Unconventional Myosins In Tetrmentioning

confidence: 99%

Myosin genes in Tetrahymena

Williams

Gavin

2005

Cell Motil. Cytoskeleton

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Section: Myosin Genes Encode Divergent Unconventional Myosins In Tetrmentioning

confidence: 99%

Myosin genes in Tetrahymena

Williams

Gavin

2005

Cell Motil. Cytoskeleton

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“…These three myosins are so named because the tail of each motor contains one or a pair of MyTH4-FERM domains. The MyTH4-FERM domains in the tail regions of myosin VII, X, and XV are believed to function as cargo binding domains of these myosins (1)(2)(3)(4)(5)(6)(7), although the molecular basis of the motor-cargo interactions are not known.…”

mentioning

confidence: 99%

Cargo recognition mechanism of myosin X revealed by the structure of its tail MyTH4-FERM tandem in complex with the DCC P3 domain

Wei

Yan

Lü

et al. 2011

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

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Myosin X (MyoX), encoded by Myo10, is a representative member of the MyTH4-FERM domain-containing myosins, and this family of unconventional myosins shares common functions in promoting formation of filopodia/stereocilia structures in many cell types with unknown mechanisms. Here, we present the structure of the MyoX MyTH4-FERM tandem in complex with the cytoplasmic tail P3 domain of the netrin receptor DCC. The structure, together with biochemical studies, reveals that the MyoX MyTH4 and FERM domains interact with each other, forming a structural and functional supramodule. Instead of forming an extended β-strand structure in other FERM binding targets, DCC_P3 forms a single α-helix and binds to the αβ-groove formed by β5 and α1 of the MyoX FERM F3 lobe. Structure-based amino acid sequence analysis reveals that the key polar residues forming the inter-MyTH4/FERM interface are absolutely conserved in all MyTH4-FERM tandem-containing proteins, suggesting that the supramodular nature of the MyTH4-FERM tandem is likely a general property for all MyTH4-FERM proteins.complex structure | tail domain A mong the unconventional myosin family members (with respect to the conventional myosin for muscle contractions), there is a subfamily, called MyTH4-FERM myosins, which includes myosin VII, X, and XV (MyoVII, MyoX, and MyoXV). These three myosins are so named because the tail of each motor contains one or a pair of MyTH4-FERM domains. The MyTH4-FERM domains in the tail regions of myosin VII, X, and XV are believed to function as cargo binding domains of these myosins (1-7), although the molecular basis of the motor-cargo interactions are not known.MyoX is perhaps the best studied MyTH4-FERM myosins (8). Its tail MyTH4-FERM tandem is implicated in binding to cargo proteins including β-integrins, microtubules, and axonal guidance receptor DCC (1-3) (Fig. 1A). MyoX is well known for its capacity in filopodial induction and elongation (9-12). The functional roles of MyoX in diverse cellular processes such as cell adhesion, cell or subcellular structure migrations, and angiogenesis (1, 3, 13-16) are likely to be related to the filopodial formation activity of the motor, because filopodia are focal points that integrate various cell signals to regulate actin cytoskeletal structures (17).A distinct structural feature of the MyoX tail is that it contains a MyTH4 domain and a FERM domain connected with a short linker. Even though FERM domains in many proteins are known to function autonomously as a versatile protein and/or lipid membrane binding modules (18), the FERM domain in MyoX seems to require its N-terminal MyTH4 domain for its cellular functions. For example, deletion of either the MyTH4 or the FERM domain abolishes the MyoX's capacity in inducing elongated filopodia formation (9,11,12). The MyTH4-FERM tandem, but not either of the isolated domains, of MyoX binds to microtubules (2). Binding of MyoX to DCC or neogenin also requires the covalent connection of the MyTH4 and FERM domains (3).These findings suggest that the in...

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“…Myo10 is an unconventional myosin that binds actin filaments (F‐actin) and microtubules through a NH2‐terminal motor domain and a myosin tail homology 4 domain, respectively 49, 50. This property makes Myo10 an unusual link between microtubules and actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Adducin‐1 is essential for spindle pole integrity through its interaction with TPX2

et al. 2018

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Bipolar spindle assembly is necessary to ensure the proper progression of cell division. Loss of spindle pole integrity leads to multipolar spindles and aberrant chromosomal segregation. However, the mechanism underlying the maintenance of spindle pole integrity remains unclear. In this study, we show that the actin‐binding protein adducin‐1 (ADD1) is phosphorylated at S726 during mitosis. S726‐phosphorylated ADD1 localizes to centrosomes, wherein it organizes into a rosette‐like structure at the pericentriolar material. ADD1 depletion causes centriole splitting and therefore results in multipolar spindles during mitosis, which can be restored by re‐expression of ADD1 and the phosphomimetic S726D mutant but not by the S726A mutant. Moreover, the phosphorylation of ADD1 at S726 is crucial for its interaction with TPX2, which is essential for spindle pole integrity. Together, our findings unveil a novel function of ADD1 in maintaining spindle pole integrity through its interaction with TPX2.

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A microtubule-binding myosin required for nuclear anchoring and spindle assembly

Cited by 235 publications

References 30 publications

Myosin genes in Tetrahymena

Myosin genes in Tetrahymena

Cargo recognition mechanism of myosin X revealed by the structure of its tail MyTH4-FERM tandem in complex with the DCC P3 domain

Adducin‐1 is essential for spindle pole integrity through its interaction with TPX2

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