Actin Tyrosine-53-Phosphorylation in Neuronal Maturation and Synaptic Plasticity

Bertling, Enni; Englund, Jonas; Minkeviciene, Rimante; Koskinen, Mikko; Segerstråle, Mikael; Ċastrén, Eero; Taira, Tomi; Hotulainen, Pirta

doi:10.1523/jneurosci.2649-15.2016

Cited by 29 publications

(22 citation statements)

References 59 publications

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“…Hippocampal dendritic spines from GFP-positive neurons were imaged with a Zeiss Axio Observer.Z1 inverted microscope (63× NA 1.4 oil objective) equipped with Zeiss LSM 800 confocal module (Carl Zeiss Microimaging GmbH, Jena, Germany). Serial Z-stacks of optical sections from dendritic segments were captured for spine analysis performed with NeuronStudio software [ 21 ] as described previously [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

DHCR24 exerts neuroprotection upon inflammation-induced neuronal death

Martiskainen

Paldanius

Natunen

et al. 2017

J Neuroinflammation

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BackgroundDHCR24, involved in the de novo synthesis of cholesterol and protection of neuronal cells against different stress conditions, has been shown to be selectively downregulated in neurons of the affected brain areas in Alzheimer’s disease.MethodsHere, we investigated whether the overexpression of DHCR24 protects neurons against inflammation-induced neuronal death using co-cultures of mouse embryonic primary cortical neurons and BV2 microglial cells upon acute neuroinflammation. Moreover, the effects of DHCR24 overexpression on dendritic spine density and morphology in cultured mature mouse hippocampal neurons and on the outcome measures of ischemia-induced brain damage in vivo in mice were assessed.ResultsOverexpression of DHCR24 reduced the loss of neurons under inflammation elicited by LPS and IFN-γ treatment in co-cultures of mouse neurons and BV2 microglial cells but did not affect the production of neuroinflammatory mediators, total cellular cholesterol levels, or the activity of proteins linked with neuroprotective signaling. Conversely, the levels of post-synaptic cell adhesion protein neuroligin-1 were significantly increased upon the overexpression of DHCR24 in basal growth conditions. Augmentation of DHCR24 also increased the total number of dendritic spines and the proportion of mushroom spines in mature mouse hippocampal neurons. In vivo, overexpression of DHCR24 in striatum reduced the lesion size measured by MRI in a mouse model of transient focal ischemia.ConclusionsThese results suggest that the augmentation of DHCR24 levels provides neuroprotection in acute stress conditions, which lead to neuronal loss in vitro and in vivo.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0991-6) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

DHCR24 exerts neuroprotection upon inflammation-induced neuronal death

Martiskainen

Paldanius

Natunen

et al. 2017

J Neuroinflammation

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“…Hippocampal dendritic spines from GFP-positive neurons were imaged with a Zeiss Axio Observer.Z1 inverted microscope (63 x NA 1.4 oil objective) equipped with Zeiss LSM 800 confocal module (Carl Zeiss Microimaging GmbH, Jena, Germany). Serial Z-stacks of optical sections from dendritic segments were captured for spine analysis performed with NeuronStudio software (Rodriguez et al, 2008) as described previously (Bertling et al, 2016).…”

Section: Mouse Primary Hippocampal Neuron Culture Transient Transfecmentioning

confidence: 99%

Protein kinase C -activating isophthalate derivatives mitigate Alzheimer's disease-related cellular alterations

et al. 2018

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Abnormal protein kinase C (PKC) function contributes to many pathophysiological processes relevant for Alzheimer's disease (AD), such as amyloid precursor protein (APP) processing. Phorbol esters and other PKC activators have been demonstrated to enhance the secretion of soluble APPα (sAPPα), reduce the levels of β-amyloid (Aβ), induce synaptogenesis, and promote neuroprotection. We have previously described isophthalate derivatives as a structurally simple family of PKC activators. Here, we characterised the effects of isophthalate derivatives HMI-1a3 and HMI-1b11 on neuronal viability, neuroinflammatory response, processing of APP and dendritic spine density and morphology in in vitro. HMI-1a3 increased the viability of embryonic primary cortical neurons and decreased the production of the pro-inflammatory mediator TNFα, but not that of nitric oxide, in mouse neuron-BV2 microglia co-cultures upon LPS- and IFN-γ-induced neuroinflammation. Furthermore, both HMI-1a3 and HMI-1b11 increased the levels of sAPPα relative to total sAPP and the ratio of Aβ42/Aβ40 in human SH-SY5Y neuroblastoma cells. Finally, bryostatin-1, but not HMI-1a3, increased the number of mushroom spines in proportion to total spine density in mature mouse hippocampal neuron cultures. These results suggest that the PKC activator HMI-1a3 exerts neuroprotective functions in the in vitro models relevant for AD by reducing the production of TNFα and increasing the secretion of neuroprotective sAPPα.

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“…Stoichiometrically, tyrosine phosphorylation is less abundant, and its detection is more difficult in global profiling although it plays an important role in regulation of neuronal maturation and synaptic plasticity [ 24 ]. Tyrosine phosphopeptides can be enriched using an antibody-based immunoprecipitation approach [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Phosphotyrosine profiling of human cerebrospinal fluid

Sathe

Renuse

et al. 2018

Clin Proteom

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BackgroundCerebrospinal fluid (CSF) is an important source of potential biomarkers that affect the brain. Biomarkers for neurodegenerative disorders are needed to assist in diagnosis, monitoring disease progression and evaluating efficacy of therapies. Recent studies have demonstrated the involvement of tyrosine kinases in neuronal cell death. Thus, neurodegeneration in the brain is related to altered tyrosine phosphorylation of proteins in the brain and identification of abnormally phosphorylated tyrosine peptides in CSF has the potential to ascertain candidate biomarkers for neurodegenerative disorders.MethodsIn this study, we used an antibody-based tyrosine phosphopeptide enrichment method coupled with high resolution Orbitrap Fusion Tribrid Lumos Fourier transform mass spectrometer to catalog tyrosine phosphorylated peptides from cerebrospinal fluid. The subset of identified tyrosine phosphorylated peptides was also validated using parallel reaction monitoring (PRM)-based targeted approach.ResultsTo date, there are no published studies on global profiling of phosphotyrosine modifications of CSF proteins. We carried out phosphotyrosine profiling of CSF using an anti-phosphotyrosine antibody-based enrichment and analysis using high resolution Orbitrap Fusion Lumos mass spectrometer. We identified 111 phosphotyrosine peptides mapping to 66 proteins, which included 24 proteins which have not been identified in CSF previously. We then validated a set of 5 tyrosine phosphorylated peptides in an independent set of CSF samples from cognitively normal subjects, using a PRM-based targeted approach.ConclusionsThe findings from this deep phosphotyrosine profiling of CSF samples have the potential to identify novel disease-related phosphotyrosine-containing peptides in CSF.Electronic supplementary materialThe online version of this article (10.1186/s12014-018-9205-1) contains supplementary material, which is available to authorized users.

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Actin Tyrosine-53-Phosphorylation in Neuronal Maturation and Synaptic Plasticity

Cited by 29 publications

References 59 publications

DHCR24 exerts neuroprotection upon inflammation-induced neuronal death

DHCR24 exerts neuroprotection upon inflammation-induced neuronal death

Protein kinase C -activating isophthalate derivatives mitigate Alzheimer's disease-related cellular alterations

Phosphotyrosine profiling of human cerebrospinal fluid

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