A detailed proteomic profiling of plasma membrane from zebrafish brain

Šmidák, Roman; Aradská, Jana; Kirchberger, Stefanie; Distel, Martin; Sialana, Fernando J.; Wackerlig, Judith; Mechtcheriakova, Diana; Lübec, Gert

doi:10.1002/prca.201600081

Cited by 9 publications

(7 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taking into account this broad spectrum of Bbs functions as well as our current results elaborating the role of Bbs, such as reduction in dendritic spine density along with aberrant synaptic IGF receptor signalling and altered neurotransmitter receptor levels (NMDA and AMPA), we hypothesised that Bbs proteins may play a vital role in neuronal synapses. Re-evaluation of our earlier mass spectrometric analyses of synaptosomal [33,34] and crude synaptosomal fractions [35] of the rat cortex, dorsal striatum, and DG revealed the presence of Bbs1, Bbs2, Bbs4, Bbs5, Bbs7, and Bbs10 proteins (S1 Table).…”

Section: Resultsmentioning

confidence: 95%

Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons

et al. 2019

Self Cite

View full text Add to dashboard Cite

Bardet-Biedl syndrome (BBS), a ciliopathy, is a rare genetic condition characterised by retinal degeneration, obesity, kidney failure, and cognitive impairment. In spite of progress made in our general understanding of BBS aetiology, the molecular and cellular mechanisms underlying cognitive impairment in BBS remain elusive. Here, we report that the loss of BBS proteins causes synaptic dysfunction in principal neurons, providing a possible explanation for the cognitive impairment phenotype observed in BBS patients. Using synaptosomal proteomics and immunocytochemistry, we demonstrate the presence of Bbs proteins in the postsynaptic density (PSD) of hippocampal neurons. Loss of Bbs results in a significant reduction of dendritic spines in principal neurons of Bbs mouse models. Furthermore, we show that spine deficiency correlates with events that destabilise spine architecture, such as impaired spine membrane receptor signalling, known to be involved in the maintenance of dendritic spines. Our findings suggest a role for BBS proteins in dendritic spine homeostasis that may be linked to the cognitive phenotype observed in BBS.

show abstract

Section: Resultsmentioning

confidence: 95%

Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The pooled sample was separated by reversed-phase liquid chromatography (RP-LC) at high pH as previously described ( Gilar et al, 2005 ) resulting in 25 fractions. The peptide fractions were analyzed by liquid chromatography-tandem mass spectrometry (LC–MS/MS) with two technical replicates per sample using the LC separation procedure described previously ( Smidak et al, 2016 ). MS analysis was performed by the Thermo Scientific TM Q Exactive TM Plus Orbitrap mass spectrometer (Thermo Scientific) in positive ion mode with full-scan MS in the range of m/z 375–1400 at the resolution of 35,000 (at m/z 200).…”

Section: Methodsmentioning

confidence: 99%

Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

Šmidák

Sialana

Kristofova

et al. 2017

Front. Aging Neurosci.

Self Cite

View full text Add to dashboard Cite

Fragile X mental retardation protein (FMRP) encoded by Fragile X mental retardation 1 (FMR1) gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS) that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal changes of FMRP in aging rats are not fully elucidated. The current study addresses the changes in FMRP levels in dentate gyrus (DG) from young (17 weeks) and aging (22 months) Sprague – Dawley rats. The aging animal group showed significant decline in spatial reference memory. Protein samples from five rats per each group were analyzed by quantitative proteomic analysis resulting in 153 significantly changed proteins. FMRP showed significant reduction in aging animals which was confirmed by immunoblotting and immunofluorescence microscopy. Furthermore, bioinformatic analysis of the differential protein dataset revealed several functionally related protein groups with individual interactions with FMRP. These include high representation of the RNA translation and processing machinery connected to FMRP and other RNA-binding regulators including CAPRIN1, the members of Pumilio (PUM) and CUG-BP, Elav-like (CELF) family, and YTH N(6)-methyladenosine RNA-binding proteins (YTHDF). The results of the current study point to the important role of FMRP and regulation of RNA processing in the rat DG and memory decline during the aging process.

show abstract

“…In zebrafish brain, multiple RNA isoforms of the ryanodine-sensitive Ca 2+ channel (Ryr) have been identified (Darbandi and Franck, 2009;Holland et al, 2017;Tse et al, 2018), but the relative protein products have been partially analyzed (Wu et al, 2011). Zebrafish Purkinje cells express the IP3-sensitive Ca 2+ channel (ITPR1) in the cell body, the axon, the dendritic shaft, and the spines (Koulen et al, 2000), and adult zebrafish brain proteomic studies have identified Casq2 protein in total homogenates (Nolte et al, 2014;Smidak et al, 2016), but cell-type expression and localization remain to be elucidated. Based on current proteomic and transcriptomic studies, it is evident that multiple isoforms of Ca 2+ store components are expressed in adult zebrafish brain so that the latter is a suitable model to identify neuronal Ca 2+ stores in different cells and compartments.…”

Section: Neuronal Er Ca 2+ Binding Proteinsmentioning

confidence: 99%

Calsequestrins New Calcium Store Markers of Adult Zebrafish Cerebellum and Optic Tectum

et al. 2020

View full text Add to dashboard Cite

Calcium stores in neurons are heterogeneous in compartmentalization and molecular composition. Danio rerio (zebrafish) is an animal model with a simply folded cerebellum similar in cellular organization to that of mammals. The aim of the study was to identify new endoplasmic reticulum (ER) calcium store markers in zebrafish adult brain with emphasis on cerebellum and optic tectum. By quantitative polymerase chain reaction, we found three RNA transcripts coding for the intra-ER calcium binding protein calsequestrin: casq1a, casq1b, and casq2. In brain homogenates, two isoforms were detected by mass spectrometry and western blotting. Fractionation experiments of whole brain revealed that Casq1a and Casq2 were enriched in a heavy fraction containing ER microsomes and synaptic membranes. By in situ hybridization, we found the heterogeneous expression of casq1a and casq2 mRNA to be compatible with the cellular localization of calsequestrins investigated by immunofluorescence. Casq1 was expressed in neurogenic differentiation 1 expressing the granule cells of the cerebellum and the periventricular zone of the optic tectum. Casq2 was concentrated in parvalbumin expressing Purkinje cells. At a subcellular level, Casq1 was restricted to granular cell bodies, and Casq2 was localized in cell bodies, dendrites, and axons. Data are discussed in relation to the differential cellular and subcellular distribution of other cerebellum calcium store markers and are evaluated with respect to the putative relevance of calsequestrins in the neuron-specific functional activity.

show abstract

A detailed proteomic profiling of plasma membrane from zebrafish brain

Cited by 9 publications

References 25 publications

Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons

Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons

Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

Calsequestrins New Calcium Store Markers of Adult Zebrafish Cerebellum and Optic Tectum

Contact Info

Product

Resources

About