Sequential roles for myosin-X in BMP6-dependent filopodial extension, migration, and activation of BMP receptors

Pi, Xinchun; Ren, Rongqin; Kelley, Russell; Zhang, Chunlian; Moser, Martin; Bohil, Aparna B.; DiVito, Melinda M.; Cheney, Richard E.; Patterson, Cam

doi:10.1083/jcb.200704010

Cited by 99 publications

(106 citation statements)

References 34 publications

(48 reference statements)

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“…To determine whether eNOS activation is required for SDF-1␣-mediated endothelial cell migration, we performed scratch wound-healing and Boyden chamber migration assays in the presence of the NOS-specific inhibitor N G -monomethyl-L-arginine (L-NMMA) (19). Conf luent BAECs were pre-treated for 1 h with 1 or 5 mM L-NMMA or vehicle before each assay.…”

Section: Results Enos Is Activated By Sdf-1␣ and Is Required For Endomentioning

confidence: 99%

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

Wu²,

Ferguson³

et al. 2009

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

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The chemokine stromal cell-derived factor-1␣ (SDF-1␣) is a pivotal player in angiogenesis. It is capable of influencing such cellular processes as tubulogenesis and endothelial cell migration, yet very little is known about the actual signaling events that mediate SDF-1␣-induced endothelial cell function. In this report, we describe the identification of an intricate SDF-1␣-induced signaling cascade that involves endothelial nitric oxide synthase (eNOS), JNK3, and MAPK phosphatase 7 (MKP7). We demonstrate that the SDF-1␣-induced activation of JNK3, critical for endothelial cell migration, depends on the prior activation of eNOS. Specifically, activation of eNOS leads to production of NO and subsequent nitrosylation of MKP7, rendering the phosphatase inactive and unable to inhibit the activation of JNK3. These observations reinforce the importance of nitric oxide and S-nitrosylation in angiogenesis and provide a mechanistic pathway for SDF-1␣-induced endothelial cell migration. In addition, the discovery of this interactive network of pathways provides novel and unexpected therapeutic targets for angiogenesis-dependent diseases.

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Section: Results Enos Is Activated By Sdf-1␣ and Is Required For Endomentioning

confidence: 99%

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

Wu²,

Ferguson³

et al. 2009

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

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“…While the role of Myo10 in regulating cellular processes is not well understood, it is known to promote filopodia formation and elongation in non-neuronal cells (Bohil et al, 2006;Pi et al, 2007;Zhang et al, 2004). In neurons, it has been demonstrated to regulate axonal pathfinding, neurite outgrowth and related processes (Ju et al, 2013;Zhu et al, 2007).…”

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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“…MyoX is well known for its capacity in filopodial induction and elongation (9)(10)(11)(12). The functional roles of MyoX in diverse cellular processes such as cell adhesion, cell or subcellular structure migrations, and angiogenesis (1,3,(13)(14)(15)(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).…”

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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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Sequential roles for myosin-X in BMP6-dependent filopodial extension, migration, and activation of BMP receptors

Cited by 99 publications

References 34 publications

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

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

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

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