Mouse <i>Prickle1</i> and <i>Prickle2</i> are expressed in postmitotic neurons and promote neurite outgrowth

Okuda, Hiromichi; Miyata, Sumiko; Mori, Yuichiro; Tohyama, Masaya

doi:10.1016/j.febslet.2007.08.075

Cited by 55 publications

(48 citation statements)

References 27 publications

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“…Recently, mammalian teneurins have been shown to be latrophilin (Lphn) receptors, which are known to mediate the massive synaptic exocytosis caused by the black widow spider venom α-latrotoxin and which also were identified as reduced in deprived synapses (48,87). Prickle2 has been shown to regulate neurite formation and outgrowth, but only in neuroblastoma cell lines (55). Further investigations into these proteins in primary mammalian synapses will provide key insights into mechanisms that lead to synaptic maturation and stability.…”

Section: Discussionmentioning

confidence: 99%

In vivo quantitative proteomics of somatosensory cortical synapses shows which protein levels are modulated by sensory deprivation

Butko¹,

Savas

Friedman³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Postnatal bilateral whisker trimming was used as a model system to test how synaptic proteomes are altered in barrel cortex by sensory deprivation during synaptogenesis. Using quantitative mass spectrometry, we quantified more than 7,000 synaptic proteins and identified 89 significantly reduced and 161 significantly elevated proteins in sensory-deprived synapses, 22 of which were validated by immunoblotting. More than 95% of quantified proteins, including abundant synaptic proteins such as PSD-95 and gephyrin, exhibited no significant difference under high-and low-activity rearing conditions, suggesting no tissue-wide changes in excitatory or inhibitory synaptic density. In contrast, several proteins that promote mature spine morphology and synaptic strength, such as excitatory glutamate receptors and known accessory factors, were reduced significantly in deprived synapses. Immunohistochemistry revealed that the reduction in SynGAP1, a postsynaptic scaffolding protein, was restricted largely to layer I of barrel cortex in sensorydeprived rats. In addition, protein-degradation machinery such as proteasome subunits, E2 ligases, and E3 ligases, accumulated significantly in deprived synapses, suggesting targeted synaptic protein degradation under sensory deprivation. Importantly, this screen identified synaptic proteins whose levels were affected by sensory deprivation but whose synaptic roles have not yet been characterized in mammalian neurons. These data demonstrate the feasibility of defining synaptic proteomes under different sensory rearing conditions and could be applied to elucidate further molecular mechanisms of sensory development. mass spectrometric proteomics | somatosensory cortex | experience-dependent plasticity | synaptic protein dynamics S ensory information is encoded in the brain by activation of specific neuronal circuits that operate via chemical synapses. Important sensory experiences are stored by strengthening activated synapses in the circuit, a process known as "experience-dependent plasticity" (1). When animals are deprived of sensory experience during development, for example, by trimming rodent whiskers from birth to 30 d after birth, synaptic strength and mature synaptic morphology are attenuated, suggesting that the low activity in the deprived circuits interferes with normal development (2-7). However, the molecular changes that alter these synaptic properties in response to experience remain unclear. Synaptic activation has been shown to promote regulated and highly localized effects on synaptic proteins such as local translation, recruitment, and targeted degradation (8-11), and this spatiotemporal control of protein availability is required for long-term plasticity and synaptic maturation, which are fundamental in memory formation and storage and ultimately for an organism's survival (12-14). The need for highly controlled protein availability is highlighted in studies of neurological diseases, which often result from the disruption of protein availability at the synapse (15-17). ...

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Section: Discussionmentioning

confidence: 99%

In vivo quantitative proteomics of somatosensory cortical synapses shows which protein levels are modulated by sensory deprivation

Butko¹,

Savas

Friedman³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Immunohistochemistry-Immunohistochemistry was performed as described previously (17). Briefly, mice were perfused with phosphate-buffered saline (PBS) (pH 7.4) followed by 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

“…In Situ Hybridization-In situ hybridization was performed as described previously (17). Partial cDNAs for mouse TNR, phosphacan, brevican, neurocan, and versican were amplified by reverse transcriptase-PCR using the following primers: partial TNR forward primer, 5Ј-AAGGGCTACAGTTCAA-GACG-3Ј (complement of nucleotides (nt) 1256 -1275); partial TNR reverse primer, 5Ј-GCTGTTATCCCATTCCAGGT-3Ј (reverse complement of nt 1888 -1907); partial phosphacan forward primer, 5Ј-AATAGCCCAAAGCAGTCTCC-3Ј (complement of nt 173-192); partial phosphacan reverse primer, 5Ј-CTTTCAGAGATGCTAACTGTATCC-3Ј (reverse complement of nt 750 -773); partial brevican forward primer, 5Ј-AGGAACTGCAGCTGCCTCAG-3Ј (complement of nt 1148 -1167); partial brevican reverse primer, 5Ј-GGTATC-GATCGTTGACAAAGTC-3Ј (reverse complement of nt 2125-2146); partial neurocan forward primer, 5Ј-AACTCTA-CGATGTCTACTGC-3Ј (complement of nt 737-756); partial neurocan reverse primer, 5Ј-TGGAGTAGAACCAAGGG-TCT-3Ј (reverse complement of nt 1277-1296); partial versican forward primer, 5Ј-GGAATCACCCACAACTAC-TCG-3Ј (complement of nt 1275-1295); partial versican reverse primer, 5Ј-CCAAACTCATCTTCAGTCACC-3Ј (reverse complement of nt .…”

Section: Methodsmentioning

confidence: 99%

“…Immunocytochemistry for Cultured Cells-Immunocytochemistry for cultured cells was performed as described previously (17). The primary antibodies used in this study were as follows: anti-TNR (dilution 1:1000, BD Transduction Laboratories), anti-glial fibrillary acidic protein (GFAP, 1:10000, DAKO), anti-S100␤ (1:2000), and CS-56 (1:300), and the secondary antibodies were biotinylated anti-mouse IgG (1:200), Alexa Fluor 546-labeled anti-rabbit IgG, and Alexa Fluor 488-labeled anti-mouse IgG (1:1000, Invitrogen).…”

Section: Quantification Of Tnr Mrna/s100␤-double Positive Cells In Thmentioning

confidence: 99%

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Chondroitin Sulfate Proteoglycan Tenascin-R Regulates Glutamate Uptake by Adult Brain Astrocytes

Okuda¹,

Tatsumi

Morita

et al. 2014

Journal of Biological Chemistry

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Background: CS-56 immunoreactivity reveals a subpopulation of astrocytes in the adult mouse cerebral cortex. Results: TNR mRNA was detected in CS-56-positive astrocytes, and TNR regulates astrocytic GLAST expression. Conclusion: TNR-expressing cells are a subpopulation of astrocytes and regulate extracellular glutamate homeostasis. Significance: Astrocytes in the adult mouse cerebral cortex exhibit a molecular and functional heterogeneity that could become future therapeutic targets in brain injury.

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“…The Wnt signaling pathway regulates a myriad of neurodevelopmental processes, e.g., cell fate determination, axon migration, dendritic arborization, and synapse formation (10)(11)(12)(13)(14)(15)(16)(17)(18). There are two major pathways that define the Wnt signaling pathway; the canonical and non-canonical pathways.…”

Section: Introductionmentioning

confidence: 99%

Erratum: Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction

Sowers¹,

Loo²,

Wu³

et al. 2013

Mol Psychiatry

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Author Contributions: LPS contributed to all experiments, planning, and writing of the paper. LL performed all in vitro electrophysiology. YW performed in vivo electrophysiology. LL, LPS and DPM analyzed all the electrophysiology data. EC performed mouse behavioral experiments. YMU and JU performed a part of primary hippocampal neuron cultures. SW performed western blot experiments. JRM, HEL, LP, TW, XY and KM aided in the collection and sequencing of human DNA. PF, NU and SW conducted production and breeding of mice of different genotypes used in this study. AJS assisted in all immunocytochemistry experiments and analysis. GBR, DPM, and JM provided reagents, supervised experiments and analysis, and aided in manuscript writing. JAW provided all behavioral equipment. JAW and DPM provided scientific input to the study design. BWD provided statistical analysis for whole exome sequencing data. All authors contributed to the writing of this manuscript. AGB supervised all aspects of the project design, execution and writing of the paper. The datasets used for the analysis described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000298.v1.p1, under dbGAP Research Project #4357 (Variation in PRICKLE2 and related Genes in Autism) to AGB. The data set(s) were deposited by the ARRA Autism Sequencing Collaborative, an ARRA funded research initiative. AbstractAutism spectrum disorders (ASDs) have been suggested to arise from abnormalities in the canonical and non-canonical Wnt signaling pathways. However, a direct connection between a human variant in a Wnt pathway gene and ASD-relevant brain pathology has not been established. Prickle2 (Pk2) is a post-synaptic non-canonical Wnt signaling protein shown to interact with post synaptic density 95 (PSD-95). Here we show that mice with disruption in Prickle2 display behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility. Prickle2 disruption in mouse hippocampal neurons led to reductions in dendrite branching, synapse number, and post-synaptic density size. Consistent with these findings, Prickle2 null neurons show decreased frequency and size of spontaneous miniature synaptic currents. These behavioral and physiological abnormalities in Prickle2 disrupted mice are consistent with ASD-like phenotypes present in other mouse models of ASDs. In 384 individuals with autism, we identified two with distinct, heterozygous, rare, non-synonymous PRICKLE2 variants (p.E8Q and p.V153I) that were shared by their affected siblings and inherited paternally. Unlike wild-type PRICKLE2, the PRICKLE2 variants found in ASD patients exhibit deficits in morphological and electrophysiological assays. These data suggest that these PRICKLE2 variants cause a critical loss of PRICKLE2 function. The data presented here provide new insight into the biological roles of Prickle2, its behavioral importance, and suggest disruptions in non-canonical Wnt genes such as PRICKLE2 may contribu...

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Mouse Prickle1 and Prickle2 are expressed in postmitotic neurons and promote neurite outgrowth

Cited by 55 publications

References 27 publications

In vivo quantitative proteomics of somatosensory cortical synapses shows which protein levels are modulated by sensory deprivation

In vivo quantitative proteomics of somatosensory cortical synapses shows which protein levels are modulated by sensory deprivation

Chondroitin Sulfate Proteoglycan Tenascin-R Regulates Glutamate Uptake by Adult Brain Astrocytes

Erratum: Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction

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