Myosin IIB Is Required for Growth Cone Motility

Bridgman, Paul C.; Davé, Sonya; Asnes, Clara F.; Tullio, Antonella N.; Adelstein, Robert S.

doi:10.1523/jneurosci.21-16-06159.2001

Cited by 193 publications

(201 citation statements)

References 45 publications

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“…2C). As in NMIIB knockout mice (27), knocking down NMIIB inhibited axon growth on permissive substrates. By contrast, depletion of NMIIA enhanced axon growth ( Fig.…”

Section: Nmii Inhibition Promotes Robust Axon Growth Over Cspgs and Cnsmentioning

confidence: 84%

“…3), and there was a dramatic reduction in the growth cone lamellipodial areas in response to blebbistatin. By contrast, filopodial structures became more prominent, reminiscent of the growth cone structures of the NMIIB knockout mice (27) and the changes in Factin structure induced by NMIIB inhibition in chicken DRG neurons (32). The structural reorganization was accompanied by reduction in the total F-actin levels.…”

Section: Axon Growth Promotion Over Cspgs Induced By Nmii Inhibitionmentioning

confidence: 99%

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Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules

Hur¹,

Yang²,

Kim³

et al. 2011

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

126

152

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Neurons in the central nervous system (CNS) fail to regenerate axons after injuries due to the diminished intrinsic axon growth capacity of mature neurons and the hostile extrinsic environment composed of a milieu of inhibitory factors. Recent studies revealed that targeting a particular group of extracellular inhibitory factors is insufficient to trigger long-distance axon regeneration. Instead of antagonizing the growing list of impediments, tackling a common target that mediates axon growth inhibition offers an alternative strategy to promote axon regeneration. Neuronal growth cone, the machinery that derives axon extension, is the final converging target of most, if not all, growth impediments in the CNS. In this study, we aim to promote axon growth by directly targeting the growth cone. Here we report that pharmacological inhibition or genetic silencing of nonmuscle myosin II (NMII) markedly accelerates axon growth over permissive and nonpermissive substrates, including major CNS inhibitors such as chondroitin sulfate proteoglycans and myelin-associated inhibitors. We find that NMII inhibition leads to the reorganization of both actin and microtubules (MTs) in the growth cone, resulting in MT reorganization that allows rapid axon extension over inhibitory substrates. In addition to enhancing axon extension, we show that local blockade of NMII activity in axons is sufficient to trigger axons to grow across the permissive-inhibitory border. Together, our study proposes NMII and growth cone cytoskeletal components as effective targets for promoting axon regeneration.myelin | glial scar | multi-compartment neuronal culture chamber

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“…2C). As in NMIIB knockout mice (27), knocking down NMIIB inhibited axon growth on permissive substrates. By contrast, depletion of NMIIA enhanced axon growth ( Fig.…”

Section: Nmii Inhibition Promotes Robust Axon Growth Over Cspgs and Cnsmentioning

confidence: 84%

Section: Axon Growth Promotion Over Cspgs Induced By Nmii Inhibitionmentioning

confidence: 99%

Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules

Hur¹,

Yang²,

Kim³

et al. 2011

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

126

152

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“…35 S-Labeled MSAP, MRLC (15), and ezrin (3) were generated by in vitro transcription and translation using the TNT T7-coupled reticulocyte lysate system (Promega). The proteins were incubated for 1 h with GST-MIR or GST.…”

Section: Methodsmentioning

confidence: 99%

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Bornhäuser¹,

Olsson

Lindholm

2003

Journal of Biological Chemistry

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Interactions between the cell membrane and the cytoskeleton play a major role in different aspects of cell differentiation, such as cell motility, cell division, and establishment of cellular architecture. Of particular importance in this context is the association of cortical actin with the cell membrane. The ERM 1 proteins, ezrin, radixin, and moesin, are members of the large 4.1 protein family and are involved in membrane-cytoskeleton interactions. They link the actin cytoskeleton to membranebound proteins located at different membrane sites, i.e. microvilli, membrane ruffles, and cell-cell contacts (1-3). This is accomplished by binding of the C-terminal part of the ERM proteins to actin and of the N-terminal FERM domain to specific membrane proteins (4). FERM domains have been found in many different proteins and are thought to be modules for protein-protein and protein-membrane interactions (5). The ERM proteins are involved in cell adhesion and signal transduction events through phosphorylation (6, 7) and interaction with phosphoinositides (8). The ERM proteins play an important role in the activation of Rho family proteins and can interact both downstream (9) and upstream (10) of Rho.In addition, the ERM proteins are involved in membrane dynamics (11). When ezrin, radixin, and moesin were simultaneously inactivated by antisense treatment in epithelial cells, cell-cell and cell-substratum adhesion was altered (12). Double suppression of radixin and moesin, but not ezrin and radixin or moesin, alters growth cone motility, inhibiting neurite extension (13). In contrast, overexpression of ezrin in insect cells leads to enhanced cell adhesion (14). The mechanisms behind these effects are, however, not well understood, but ERM proteins are known to interact with various proteins such as CD44 and ICAM-1, -2, and -3, which helps in establishing membrane specializations (for review, see Ref. 7). The identification and characterization of further binding partners for ERM proteins can give new insights into the function of these proteins.We have recently identified a novel ERM family protein, MIR, which has an ERM domain at the N terminus and lacks actin binding, instead possessing a RING domain in the Cterminal region (15). Overexpression of MIR abrogated neurite outgrowth in PC12 cells, an effect that may be brought about by its interaction with the myosin regulatory light chain (MRLC). We describe here a novel protein interacting with MIR, called MIR-interacting saposin-like protein (MSAP), which stimulates neurite outgrowth. Sequence comparisons showed that MSAP contains a saposin domain, which is found, among others, in the sphingolipid activator proteins, the saposins (16), and in some saposin-like proteins with a similar structure (17). The effects of MSAP on neurite outgrowth were reduced by MIR. MIR was shown to induce a decrease in the levels of MRLC, which could be blocked by overexpression of MSAP or by inhibition of proteasome activity. Evidence was obtained that the decrease in MRLC levels by MIR invo...

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“…IIA and IIB are differentially localized and regulated in many cell types; much less is known about the IIC isoform. In neuronal growth cones, myosin IIB is localized at the periphery (Rochlin et al, 1995) and promotes growth cone extension (Bridgman et al, 2001) independent of MLC phosphorylation (Jalink et al, 1994;Wylie and Chantler, 2001). Myosin IIA is concentrated in the central domain (Rochlin et al, 1995) where it is essential for focal contacts and may promote neurite retraction in a Rho-and MLC phosphorylation-dependent manner (Wylie et al, 1998;Wylie and Chantler, 2001).…”

Section: Role Of Rock In Myelin Sheath Formationmentioning

confidence: 99%

Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains

Melendez‐Vasquez

Einheber²,

Salzer³

2004

J. Neurosci.

105

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The myelin sheath forms by the spiral wrapping of a glial membrane around an axon. The mechanisms involved are poorly understood but are likely to involve coordinated changes in the glial cell cytoskeleton. Because of its key role as a regulator of the cytoskeleton, we investigated the role of Rho kinase (ROCK), a major downstream effector of Rho, in Schwann cell morphology, differentiation, and myelination. Pharmacologic inhibition of ROCK activity results in loss of microvilli and stress fibers in Schwann cell cultures and strikingly aberrant myelination in Schwann cell-neuron cocultures; there was no effect on Schwann cell proliferation or differentiation. Treated Schwann cells branch aberrantly and form multiple, small, independent myelin segments along the length of axons, each with associated nodes and paranodes. This organization partially resembles myelin formed by oligodendrocytes rather than the single long myelin sheath characteristic of Schwann cells. ROCK regulates myosin light chain phosphorylation, which is robustly, but transiently, activated at the onset of myelination. These results support a key role of Rho through its effector ROCK in coordinating the movement of the glial membrane around the axon at the onset of myelination via regulation of myosin phosphorylation and actomyosin assembly. They also indicate that the molecular machinery that promotes the wrapping of the glial membrane sheath around the axon is distributed along the entire length of the internode.

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Myosin IIB Is Required for Growth Cone Motility

Cited by 193 publications

References 45 publications

Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules

Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains

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