Regulation of actomyosin contractility by PI3K in sensory axons

Orlova, I. A.; Silver, Lee D.; Gallo, Gianluca

doi:10.1002/dneu.20558

Cited by 17 publications

(25 citation statements)

References 30 publications

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“…In our own work on cultured sensory neurons, we have observed that spontaneously formed, and NGF-induced, axonal filopodia also emerge from transient accumulations of actin filaments in axons [ Fig. 4(A); Loudon et al, 2006;Gallo, 2006;Orlova et al, 2007;Ketschek and Gallo, 2010]. Similarly, Mingorance-Le Meur and O'Connor (2009) and Korobova and Svitkina (2008) also report that axonal filopodia emerge from focal accumulations of axonal actin filaments.…”

Section: The Formation Of Axonal Filopodiamentioning

confidence: 73%

“…actin patches (Lau et al, 1999). In peripheral sensory neurons (Loudon et al, 2006;Gallo, 2006;Orlova et al, 2007;Ketschek and Gallo, 2010) and central nervous system neurons (Mingorance-Le Meur and O'Connor, 2009), only a fraction of actin patches spontaneously give rise to filopodia. As determined by PREM (Svitkina, 2007) actin patches in sensory axons represent accumulation of actin filaments in a meshwork type of organization ( Fig.…”

Section: The Formation Of Axonal Filopodiamentioning

confidence: 99%

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The cytoskeletal and signaling mechanisms of axon collateral branching

Gallo

2011

Developmental Neurobiology

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During development, axons are guided to their appropriate targets by a variety of guidance factors. On arriving at their synaptic targets, or while en route, axons form branches. Branches generated de novo from the main axon are termed collateral branches. The generation of axon collateral branches allows individual neurons to make contacts with multiple neurons within a target and with multiple targets. In the adult nervous system, the formation of axon collateral branches is associated with injury and disease states and may contribute to normally occurring plasticity. Collateral branches are initiated by actin filament– based axonal protrusions that subsequently become invaded by microtubules, thereby allowing the branch to mature and continue extending. This article reviews the current knowledge of the cellular mechanisms of the formation of axon collateral branches. The major conclusions of this review are (1) the mechanisms of axon extension and branching are not identical; (2) active suppression of protrusive activity along the axon negatively regulates branching; (3) the earliest steps in the formation of axon branches involve focal activation of signaling pathways within axons, which in turn drive the formation of actin-based protrusions; and (4) regulation of the microtubule array by microtubule-associated and severing proteins underlies the development of branches. Linking the activation of signaling pathways to specific proteins that directly regulate the axonal cytoskeleton underlying the formation of collateral branches remains a frontier in the field.

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Section: The Formation Of Axonal Filopodiamentioning

confidence: 73%

Section: The Formation Of Axonal Filopodiamentioning

confidence: 99%

The cytoskeletal and signaling mechanisms of axon collateral branching

Gallo

2011

Developmental Neurobiology

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164

233

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“…PI3K is an established component of the Sema3A signaling pathway (Atwal et al, 2003;Chadborn et al, 2006;Cosker and Eickholt, 2007;Orlova et al, 2007). Sema3A inactivates PI3K, and PI3K inactivation contributes to the collapse of sensory growth cones.…”

Section: Inactivation Of Pi3k By Semaphorin 3a Mediates the Loss Of Ementioning

confidence: 99%

Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K

Gallo

2008

Developmental Neurobiology

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Ezrin-radixin-moesin (ERM) proteins are involved in the linkage of membranes to theactin filament (F-actin) cytoskeleton. Phosphorylation of the C-terminus activates the F-actin binding domain of ERM proteins by preventing the action of an autoinhibitory domain. In this study, we investigated whether a growth cone collapsing signal, semaphorin 3A (Sema3A), alters the state of ERM C-terminus phosphorylation. In the growth cones of dorsal root ganglion axons, phosphorylated ERM proteins localize to filopodia. We report that Sema3A inhibits ERM protein phosphorylation in growth cone filopodia. Significantly, Sema3A decreased ERM phosphorylation prior to the onset of growth cone collapse. Over-expression of the F-actin binding fragment of ERM proteins, which competes with endogenous ERM proteins for binding to F-actin, inhibited filopodial initiation and dynamics. Sema3A has been previously shown to inhibit phosphoinositide 3-kinase (PI3K) activity. Inhibition of PI3K resulted in the loss of phosphorylated ERM proteins from growth cone filopodia, and treatment with a PI3K activating peptide blocked the effects of Sema3A on ERM phosphorylation. Collectively, these observations demonstrate that inactivation of PI3K in response to Sema3A results in decreased phosphorylation of ERM proteins in filopodia thereby contributing to growth cone collapse.

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“…Suppression of the basal activity of phosphatidylinositol 3-kinase (PI3K) is known to be required for Sema3A-induced growth cone collapse and neurite retraction (Chadborn et al, 2006;Orlova et al, 2007). Interestingly, PI3K is also known as a mediator of macropinocytosis (Swanson and Watts, 1995).…”

Section: Sema3a Signaling Decreases Syx1b Protein Levelmentioning

confidence: 99%

Syntaxin 1B Suppresses Macropinocytosis and Semaphorin 3A-Induced Growth Cone Collapse

Kabayama

Takeuchi²,

Taniguchi³

et al. 2011

J. Neurosci.

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Growth cone collapse is a crucial process for repulsive axon guidance and is accompanied by a reduction in growth cone surface area. This process of reduction may be regulated by endocytosis; however, its molecular mechanism is unclear. Macropinocytosis is a clathrinindependent form of endocytosis in which large areas of plasma membrane can be engulfed. We have reported previously that macropinocytosis is induced in growth cones of chick dorsal root ganglion neurons by semaphorin 3A (Sema3A), a repulsive axon guidance cue, and that Sema3A-induced reduction in growth cone surface area and macropinocytic vacuole area were correlated, suggesting a positive role for macropinocytosis in Sema3A-induced growth cone collapse. In the present study, we found that syntaxin 1B (Syx1B), a membrane trafficking protein, is a negative regulator of macropinocytosis, and its expression is downregulated by Sema3A signaling. Macropinocytosis inhibitor ethylisopropylamiloride or Syx1B overexpression suppressed Sema3A-induced macropinocytosis and growth cone collapse. These results indicate that Syx1B couples macropinocytosis-mediated massive internalization of the plasma membrane to Sema3A-induced growth cone collapse.

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Regulation of actomyosin contractility by PI3K in sensory axons

Cited by 17 publications

References 30 publications

The cytoskeletal and signaling mechanisms of axon collateral branching

The cytoskeletal and signaling mechanisms of axon collateral branching

Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K

Syntaxin 1B Suppresses Macropinocytosis and Semaphorin 3A-Induced Growth Cone Collapse

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