Repulsive axon guidance cues ephrin‐A2 and slit3 stop protrusion of the growth cone leading margin concurrently with inhibition of ADF/cofilin and ERM proteins

Marsick, Bonnie M.; Roche, Florence K.; Letourneau, Paul C.

doi:10.1002/cm.21016

Cited by 13 publications

(16 citation statements)

References 44 publications

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“…; Marsick et al . ); Semaphorins for their negative regulation (Nakamura et al . ), and brain‐derived neurophic factor for its small role in 5‐HTergic neurons (Garcia et al .…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine induces vascular endothelial growth factor/Netrin over‐expression via the mediation of hypoxia‐inducible factor 1‐alpha in SH‐SY5Y cells

Wang

Zhou

et al. 2016

Journal of Neurochemistry

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Fluoxetine has become one of the most promising drugs for improving clinical outcome in patients with cerebral infarction. Although the clinical efficacy of fluoxetine has been preliminarily demonstrated, its mechanism remains unclear. Hypoxiainducible factor 1-alpha (HIF-1a) is upstream to Netrin and vascular endothelial growth factor (VEGF), and under hypoxia conditions it may induce expression of Netrin-1 and VEGF in vascular endothelial cells. We sought to explore whether it can regulate their expression in hypoxia and mediate the effect of fluoxetine in hypoxia. In this study, the effect of hypoxia on the expression of VEGF and Netrin was observed in vitro by realtime PCR and western blotting in SH-SY5Y cells; the binding sites of HIF-1a in VEGF and Netrin gene promoters were identified by luciferase reporter; the effect of fluoxetine on binding of HIF-1a with Netrin and VEGF promoters in hypoxia was observed by Chromatin Immunoprecipitation (ChIP) Assay. We prove that HIF-1a regulates transcription of both VEGF and Netrin, and that in hypoxia fluoxetine up-regulates VEGF and Netrin expression via mediation of HIF-1a that binds to hypoxia-response element sites of VEGF and Netrin promoters. Our study indicates that HIF-1a may play an important role in the treatment of cerebral infarction through mediating the recovery of neurological function induced by fluoxetine, which provides theoretical basis for the development of gene therapeutic drugs targeting HIF-1a. Keywords: fluoxetine, hypoxia-inducible factor 1-alpha, ischemic infarction, netrin, vascular endothelial growth factor. Cerebral infarction is a clinically common disorder of nerve function impairment for which the most effective treatment is thrombolytic therapy at acute stage. As a key part of clinical management, the recovery treatment for damaged neurological function during infarction convalescence stage still lacks drugs with demonstrated efficacy. Among the possible drugs, monoamines are supposed to be the most promising ones. A number of animal experiments suggest that selective serotonin reuptake inhibitors (SSRIs) (Liepert 2008), which bind to 5-hydroxytryptophamine (5-HT) transporter and inhibit 5-HT reuptake thus increasing 5-HT levels at synaptic cleft, may protect injured ischemic brain tissue and promote regeneration of hippocampal neurons (Li et al. 2009;Lim et al. 2009). Some small studies suggest that these drugs may improve motor function (Loubinoux et al. 2002). Among SSRIs, fluoxetine is the one most extensively used in management of various depression symptoms. Important progress was made in 2011 with a randomized, placebocontrolled trial, Fluoxetine for Motor Recovery after Acute Received October 22, 2015; revised manuscript received December 2, 2015; accepted December 21, 2015.Address correspondence and reprint requests to Qiaoshu Wang, MD, PhD, Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China. E-mail: qwang624@139.com 1 These...

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“…; Marsick et al . ); Semaphorins for their negative regulation (Nakamura et al . ), and brain‐derived neurophic factor for its small role in 5‐HTergic neurons (Garcia et al .…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine induces vascular endothelial growth factor/Netrin over‐expression via the mediation of hypoxia‐inducible factor 1‐alpha in SH‐SY5Y cells

Wang

Zhou

et al. 2016

Journal of Neurochemistry

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“…On the other hand, in chick embryonic neurons, three repulsive cues, slit3, ephrin‐A2, and semaphorin 3A, also inhibit cofilin (increase phospho‐ADF/cofilin), consistent with RhoA activation by these cues (Marsick et al . ). This decreased ADF/cofilin activity in slit3‐ or ephrin‐A2‐treated growth cones is associated with a reduction in F‐actin barbed ends, which are seeds for actin polymerization.…”

Section: Signal Transduction Pathways That Regulate Actin Filament Dymentioning

confidence: 97%

“…; Marsick et al . ; Sarmiere and Bamburg ;). Excess ADF/cofilin activity can promote extensive filament breakdown, however, when G‐actin concentrations are high, balanced ADF/cofilin activity can create limited F‐actin severing, and the increase in barbed ends will trigger accelerated actin polymerization and protrusion.…”

Section: Roles Of Abps In Filopodial and Lamellipodial Protrusionmentioning

confidence: 99%

Actin dynamics in growth cone motility and navigation

Gómez

Letourneau

2013

Journal of Neurochemistry

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209

186

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Motile growth cones lead growing axons through developing tissues to synaptic targets. These behaviors depend on the organization and dynamics of actin filaments that fill the growth cone leading margin (peripheral (P-) domain). Actin filament organization in growth cones is regulated by actin-binding proteins that control all aspects of filament assembly, turnover, interactions with other filaments and cytoplasmic components, and participation in producing mechanical forces. Actin filament polymerization drives protrusion of sensory filopodia and lamellipodia, and actin filament connections to the plasma membrane link the filament network to adhesive contacts of filopodia and lamellipodia with other surfaces. These contacts stabilize protrusions and transduce mechanical forces generated by actomyosin activity into traction that pulls an elongating axon along the path towards its target. Adhesive ligands and extrinsic guidance cues bind growth cone receptors and trigger signaling activities involving Rho GTPases, kinases, phosphatases, cyclic nucleotides and [Ca++] fluxes. These signals regulate actin binding proteins to locally modulate actin polymerization, interactions and force transduction to steer the growth cone leading margin towards the sources of attractive cues and away from repellent guidance cues.

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“…ROCK can phosphorylate and activate LIMK1, leading to the inactivation of cofilin. Such a pathway has been indicated in growth cone inhibition by several repulsive cues (Aizawa et al, 2001; Marsick et al, 2012). In this case, however, inhibition of growth cone motility is likely achieved through the activation of the actomyosin contractility through ROCK activation of myosin light chain kinase (Amano et al, 1998; Kubo et al, 2008).…”

Section: The Dynamic Actin Cytoskeleton In Axon Elongation and Guidancementioning

confidence: 99%

Actin-based growth cone motility and guidance

Omotade

Pollitt

Zheng

2017

Molecular and Cellular Neuroscience

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Nerve growth cones, the dilated tip of developing axons, are equipped with exquisite abilities to sense environmental cues and to move rapidly through complex terrains of developing brain, leading the axons to their specific targets for precise neuronal wiring. The actin cytoskeleton is the major component of the growth cone that powers its directional motility. Past research has provided significant insights into the mechanisms by which growth cones translate extracellular signals into directional migration. In this review, we summarize the actin-based mechanisms underlying directional growth cone motility, examine novel findings, and discuss the outstanding questions concerning the actin-based growth cone behaviors.

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Repulsive axon guidance cues ephrin‐A2 and slit3 stop protrusion of the growth cone leading margin concurrently with inhibition of ADF/cofilin and ERM proteins

Cited by 13 publications

References 44 publications

Fluoxetine induces vascular endothelial growth factor/Netrin over‐expression via the mediation of hypoxia‐inducible factor 1‐alpha in SH‐SY5Y cells

Fluoxetine induces vascular endothelial growth factor/Netrin over‐expression via the mediation of hypoxia‐inducible factor 1‐alpha in SH‐SY5Y cells

Actin dynamics in growth cone motility and navigation

Actin-based growth cone motility and guidance

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