The THO Complex Coordinates Transcripts for Synapse Development and Dopamine Neuron Survival

Maeder, Céline I.; Kim, Jae‐Ick; Liang, Xing; Kaganovsky, Konstantin; Shen, Ao; Li, Qin; Li, Zhaoyu; Wang, Sui; Xu, X.Z. Shawn; Xiang, Yang; Ding, Jun; Shen, Kang

doi:10.1016/j.cell.2018.07.046

Cited by 32 publications

(23 citation statements)

References 55 publications

(94 reference statements)

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“…Considering cells involved in the context of locomotion control and food responses, with numerous connections to AVK, a network becomes apparent, comprising the neurons AVK and DVA, downstream SMB (connected to AVK and DVA by electrical and chemical synapses), and upstream dopaminergic PDE (Figure 6A). PDE neurons sense the texture of bacteria and, jointly with CEP and ADE neurons, are involved in the ''basal slowing response'' when animals enter a bacterial lawn (Maeder et al, 2018;Sawin et al, 2000).…”

Section: Avk Resides Within Neural Circuits Regulatingmentioning

confidence: 99%

“…If no food is found, after 10 min, behavior is altered to long, straight runs, covering larger distances (dispersal; Bhattacharya et al, 2014;Gray et al, 2005). Upon food encounter, DA is released by mechanoreceptive CEP and ADE head neurons (Kang et al, 2010) and from the midbody PDE neurons (Maeder et al, 2018). On food, animals switch to a behavior termed dwelling: slow, mostly forward locomotion with frequent reversals (Flavell et al, 2013;Fujiwara et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network

Oranth

Schultheis

Tolstenkov

et al. 2018

Neuron

147

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Graphical Abstract Highlights d Presence or absence of food promotes the dwelling or dispersal behavior of C. elegans d Dopamine signals to peptidergic interneurons in response to food d Peptidergic interneurons antagonize each other to inhibit or excite motoneurons d Cholecystokinin and RFamide modulate motoneurons to generate food response behavior SUMMARY Finding food and remaining at a food source are crucial survival strategies. We show how neural circuits and signaling molecules regulate these foodrelated behaviors in Caenorhabditis elegans. In the absence of food, AVK interneurons release FLP-1 neuropeptides that inhibit motorneurons to regulate body posture and velocity, thereby promoting dispersal. Conversely, AVK photoinhibition promoted dwelling behavior. We identified FLP-1 receptors required for these effects in distinct motoneurons. The DVA interneuron antagonizes signaling from AVK by releasing cholecystokinin-like neuropeptides that potentiate cholinergic neurons, in response to dopaminergic neurons that sense food. Dopamine also acts directly on AVK via an inhibitory dopamine receptor. Both AVK and DVA couple to head motoneurons by electrical and chemical synapses to orchestrate either dispersal or dwelling behavior, thus integrating environmental and proprioceptive signals. Dopaminergic regulation of foodrelated behavior, via similar neuropeptides, may be conserved in mammals.

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Section: Avk Resides Within Neural Circuits Regulatingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network

Oranth

Schultheis

Tolstenkov

et al. 2018

Neuron

147

View full text Add to dashboard Cite

show abstract

“…Some studies also showed regulation of CREB/CRH-1 by KIN-1/KIN-2, the nematode homologs of the regulatory and catalytic subunits of cAMP-dependent kinase PK-A (Rojo Romanos et al 2017), which might determine the speed of developmental modifications in some neurons in the nerve cord (Yu et al 2017). At least in some scenarios (such as synapse development in the nematode) PK-A -regulated CREB/CRH-1 activity is independent of CRTC, further supporting the division of CREB functions into subgroups of target genes, only some of which requiring CRTC (Maeder et al 2018). Similarly, CBP/CBP-1 cooperates with CREB/CRH-1 in many cells (Eastburn and Han 2005), and protects neurons from polyglutamine-induced neurodegeneration (Bates et al 2006).…”

mentioning

confidence: 98%

Non-Canonical Activation of CREB Mediates Neuroprotection in aC. elegansModel of Excitotoxic Necrosis

Chowdhury

Becker

et al. 2018

Preprint

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Excitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu-Receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingly, signaling downstream of GluRs can also activate neuroprotective pathways. The strongest evidence involves activation of the transcription factor cAMP Response Element Binding-protein (CREB), widely recognized for its importance in synaptic plasticity. Canonical views describe CREB as a phosphorylation-triggered transcription factor, where transcriptional activation involves CREB phosphorylation and association with CREB Binding Protein (CBP). However, given CREB’s ubiquitous cross-tissue expression, the multitude of cascades leading to CREB phosphorylation, and its ability to regulate thousands of genes, it remains unclear how CREB exerts closely-tailored, differential neuroprotective responses in excitotoxicity. A non-canonical, alternative cascade for activation of CREB-mediated transcription involves the CREB co-factor cAMP-regulated transcriptional co-activator (CRTC), and may be independent of CREB phosphorylation. To identify cascades that activate CREB in excitotoxicity we use a C. elegans model of neurodegeneration by excitotoxic necrosis. We demonstrate that CREB’s neuroprotective effect is conserved, and seems most effective in neurons with moderate Glu exposure. We find that factors mediating canonical CREB activation are not involved. Instead, phosphorylation-independent CREB activation in nematode excitotoxic necrosis hinges on CRTC. CREB-mediated transcription that depends on CRTC, but not on CREB phosphorylation, might lead to expression of a specific subset of neuroprotective genes. Elucidating conserved mechanisms of excitotoxicity-specific CREB activation can help us focus on core neuroprotective programs in excitotoxicity.

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“…There were 40 overlapping blood-secretory proteins between PPD and AutismKB database ( Figure 4C , Supplementary Table 9 ). After literature survey on the four genes, we found that RARS and THOC5 had been reported related to brain development ( 35 , 36 ).…”

Section: Resultsmentioning

confidence: 97%

Protein Biomarkers of Autism Spectrum Disorder Identified by Computational and Experimental Methods

et al. 2021

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Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects millions of people worldwide. However, there are currently no reliable biomarkers for ASD diagnosis.Materials and Methods: The strategy of computational prediction combined with experimental verification was used to identify blood protein biomarkers for ASD. First, brain tissue–based transcriptome data of ASD were collected from Gene Expression Omnibus database and analyzed to find ASD-related genes by bioinformatics method of significance analysis of microarrays. Then, a prediction program of blood-secretory proteins was applied on these genes to predict ASD-related proteins in blood. Furthermore, ELISA was used to verify these proteins in plasma samples of ASD patients.Results: A total of 364 genes were identified differentially expressed in brain tissue of ASD, among which 59 genes were predicted to encode ASD-related blood-secretory proteins. After functional analysis and literature survey, six proteins were chosen for experimental verification and five were successfully validated. Receiver operating characteristic curve analyses showed that the area under the curve of SLC25A12, LIMK1, and RARS was larger than 0.85, indicating that they are more powerful in discriminating ASD cases from controls.Conclusion: SLC25A12, LIMK1, and RARS might serve as new potential blood protein biomarkers for ASD. Our findings provide new insights into the pathogenesis and diagnosis of ASD.

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The THO Complex Coordinates Transcripts for Synapse Development and Dopamine Neuron Survival

Cited by 32 publications

References 55 publications

Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network

Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network

Non-Canonical Activation of CREB Mediates Neuroprotection in aC. elegansModel of Excitotoxic Necrosis

Protein Biomarkers of Autism Spectrum Disorder Identified by Computational and Experimental Methods

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