Y-P30 promotes axonal growth by stabilizing growth cones

Neumann, Janine R.; Dash-Wagh, Suvarna; Jüngling, Kay; Tsai, Teresa; Meschkat, Martin; Räk, Andrea; Schönfelder, Sabine; Riedel, Christian; Hamad, Mohammad I. K.; Wiese, Stefan; Pape, Hans‐Christian; Gottmann, Kurt; Kreutz, Michael R.; Wahle, Petra

doi:10.1007/s00429-014-0764-2

Cited by 5 publications

(12 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several cellular signals have been reported to be involved in the regulation of neuronal morphology, such as extracellular signal-regulated kinase (ERK) and Growth Associated Protein 43(GAP-43) 15. We examined the expression profiling of two critical proteins, ERK and GAP-43, in miR-196a transgenic mice, and the expression levels were significantly increased in miR-196a transgenic mice (Supplementary Figure 2A and 2B), suggesting miR-196a could enhance neuronal morphology via increases in ERK and GAP43 signaling.…”

Section: Resultsmentioning

confidence: 99%

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

Her¹,

Mao²,

Chang³

et al. 2017

Theranostics

View full text Add to dashboard Cite

MicroRNAs (miRNAs) play important roles in several neurobiological processes, including the development and progression of diseases. Previously, we identified that one specific miRNA, miR-196a, provides neuroprotective effects on Huntington's disease (HD), although the detailed mechanism is still unclear. Based on our bioinformatic analyses, we hypothesize miR-196a might offer neuroprotective functions through improving cytoskeletons of brain cells. Here, we show that miR-196a could enhance neuronal morphology, further ameliorating intracellular transport, synaptic plasticity, neuronal activity, and learning and memory abilities. Additionally, we found that miR-196a could suppress the expression of RAN binding protein 10 (RANBP10) through binding to its 3' untranslated region, and higher expression of RANBP10 exacerbates neuronal morphology and intracellular transport. Furthermore, miR-196a enhances neuronal morphology through suppressing RANBP10 and increasing the ability of β-tubulin polymerization. Most importantly, we observed higher expression of RANBP10 in the brains of HD transgenic mice, and higher expression of RANBP10 might exacerbate the pathological aggregates in HD. Taken together, we provide evidence that enhancement of neuronal morphology through RANBP10 is one of the neuroprotective mechanisms for miR-196a. Since miR-196a has also been reported in other neuronal diseases, this study might offer insights with regard to the therapeutic use of miR-196a in other neuronal diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

Her¹,

Mao²,

Chang³

et al. 2017

Theranostics

View full text Add to dashboard Cite

show abstract

“…Y-P30 is a ligand which enhances the interaction of the neurite growth-promoting matrix protein pleiotrophin and membrane-bound syndecan-2 and syndecan-3 [11]. Syndecan-3 is enriched on axons, and Y-P30 has been shown to promote axonal growth in a syndecan-3-dependent and heparan-sufate side chain-dependent manner in cortical stem cell-derived neurons, and in days-in-vitro (DIV) 3–4 retinal and cortical microexplants [11–13]. In immature neurons, ligand binding to syndecans, including that of Y-P30, activates Y418 c-Src phosphorylation and evokes a Src-dependent activation of p42/44 ERK kinase [13, 14].…”

Section: Introductionmentioning

confidence: 99%

“…Syndecan-3 is enriched on axons, and Y-P30 has been shown to promote axonal growth in a syndecan-3-dependent and heparan-sufate side chain-dependent manner in cortical stem cell-derived neurons, and in days-in-vitro (DIV) 3–4 retinal and cortical microexplants [11–13]. In immature neurons, ligand binding to syndecans, including that of Y-P30, activates Y418 c-Src phosphorylation and evokes a Src-dependent activation of p42/44 ERK kinase [13, 14]. Y-P30 increases the levels of active Src kinase and F-actin in cortical axonal growth cones, leading to their stabilization against collapse-inducing semaphorin-3a [13].…”

Section: Introductionmentioning

confidence: 99%

“…In immature neurons, ligand binding to syndecans, including that of Y-P30, activates Y418 c-Src phosphorylation and evokes a Src-dependent activation of p42/44 ERK kinase [13, 14]. Y-P30 increases the levels of active Src kinase and F-actin in cortical axonal growth cones, leading to their stabilization against collapse-inducing semaphorin-3a [13]. With ongoing development, syndecan-2 becomes the dominant isoform being enriched in dendritic spines [15, 16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The primate-specific peptide Y-P30 regulates morphological maturation of neocortical dendritic spines

et al. 2019

Self Cite

View full text Add to dashboard Cite

The 30-amino acid peptide Y-P30 corresponds to the N-terminus of the primate-specific, sweat gland-derived dermcidin prepropeptide. Previous work has revealed that Y-P30 enhances the interaction of pleiotrophin and syndecans-2/3, and thus represents a natural ligand to study this signaling pathway. In immature neurons, Y-P30 activates the c-Src and p42/44 ERK kinase pathway, increases the amount of F-actin in axonal growth cones, and promotes neuronal survival, cell migration and axonal elongation. The action of Y-P30 on axonal growth requires syndecan-3 and heparan sulfate side chains. Whether Y-P30 has the potential to influence dendrites and dendritic protrusions has not been explored. The latter is suggested by the observations that syndecan-2 expression increases during postnatal development, that syndecan-2 becomes enriched in dendritic spines, and that overexpression of syndecan-2 in immature neurons results in a premature morphological maturation of dendritic spines. Here, analysing rat cortical pyramidal and non-pyramidal neurons in organotypic cultures, we show that Y-P30 does not alter the development of the dendritic arborization patterns. However, Y-P30 treatment decreases the density of apical, but not basal dendritic protrusions at the expense of the filopodia. Analysis of spine morphology revealed an unchanged mushroom/stubby-to-thin spine ratio and a shortening of the longest decile of dendritic protrusions. Whole-cell recordings from cortical principal neurons in dissociated cultures grown in the presence of Y-P30 demonstrated a decrease in the frequency of glutamatergic mEPSCs. Despite these differences in protrusion morphology and synaptic transmission, the latter likely attributable to presynaptic effects, calcium event rate and amplitude recorded in pyramidal neurons in organotypic cultures were not altered by Y-P30 treatment. Together, our data suggest that Y-P30 has the capacity to decelerate spinogenesis and to promote morphological, but not synaptic, maturation of dendritic protrusions.

show abstract

“…Examples of upregulated proteins in Paper II that indicate neuroprotective function is transthyretin in the PHZ and dermcidin in the SNX. Previous preclinical studies have shown transthyretin to be neuroprotective following ICH (295)(296)(297)(298) and dermcidin to be protective against oxidative damage in in vitro and in animal models (299)(300)(301)(302). The role of such proteins in the pathophysiology of ICH needs to be further explored in future research.…”

Section: Figure 61 Protein Increase Mechanismsmentioning

confidence: 99%

Surgically Treated Intracerebral Haemorrhage : Pathophysiology and Clinical Aspects

Tobieson

2019

Linköping University Medical Dissertations

View full text Add to dashboard Cite

To Ester!If it doesn't challenge you it doesn't change you! /the inside of my Ironman cap  Abstract i ABSTRACT Mortality and morbidity of intracerebral haemorrhage (ICH) is excessively high, and the case fatality rate has not improved in the last decades. Although surgery for ICH can be life-saving, no positive effect on functional outcome has been found in large cohorts of ICH patients. Increased understanding of the pathophysiology of ICH is needed to develop improved treatment strategies. Svensk sammanfattningiii KIRURGISK BEHANDLING AV HJÄRN-BLÖDNINGAR Spontan primär hjärnblödning (ICH), som inte beror på pulsåderbråck, utgör ca 12.5% av alla strokeinsjuknanden per år i Sverige, och står för en ansenlig del av den årliga stroke-relaterade dödligheten och förlusten av funktion. Endast en liten del av patienterna kan rehabiliteras åter till ett självständigt liv. I dagsläget saknas effektiv behandling utöver att förebygga att blödningen ökar i storlek genom snabb korrigering av koagulationsrubbningar och blodtryckssänkande behandling. Ca 5 % av alla ICH i Sverige opereras, men det saknas tydlig evidens för nyttan av kirurgi utöver som livräddande åtgärd.(ii-iii) Mikrodialys är en användbar metod för att studera hjärnskada efter ICH och kan kombineras med proteomik analys men det finns fallgropar och svårigheter med tekniken att ta hänsyn till, såsom att proteiner fastnar på mikrodialysmembranet.(iv) Den nationsövergripande genomgången av kirurgiskt behandlade ICH patienter påvisar likheter avseende patienternas ålder och medvetandegrad, men skillnader i volym och lokalisation av opererade blödningar, samt i den postoperativa vården. Dessa skillnader bör vara fokus för framtida forskningsstudier för att möjliggöra utformningen av bättre riktlinjer för klinisk praxis.

show abstract

Y-P30 promotes axonal growth by stabilizing growth cones

Cited by 5 publications

References 48 publications

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

The primate-specific peptide Y-P30 regulates morphological maturation of neocortical dendritic spines

Surgically Treated Intracerebral Haemorrhage : Pathophysiology and Clinical Aspects

Contact Info

Product

Resources

About