Actin and Actin-Binding Proteins: Masters of Dendritic Spine Formation, Morphology, and Function

Lin, Wan-Hsin; Webb, Donna J.

doi:10.2174/1874082000903010054

Cited by 11 publications

(12 citation statements)

References 155 publications

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“…Figure 4D shows the top functional annotations for modules 10 and 14, as revealed by a high DRaWR percentile score in every species, and with additional support from standard enrichment tests (hypergeometric test nominal p-value ≤ 0.05) in at least two of the three species. Module 14 comprises genes involved in cell-matrix adhesion, a process involved in neural development and plasticity (Murase & Schuman 1999); Rho GTPase binding, a process implicated in several aspects of neuronal development as well as neurological diseases (Govek et al 2005); and actin binding, a process associated with function and plasticity of dendritic spines and synapses (Lin & Webb, 2009). Module 10 includes genes annotated for AMP deaminase activity and IMP biosynthesis, processes associated with purine balance in the brain.…”

Section: Materials and Methods)mentioning

confidence: 99%

Cross-species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

Saul

Blatti

Yang

et al. 2017

Preprint

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Behavioral responses to social challenges like territorial intrusion occur in widely diverging species. Recent work has suggested that evolutionary "toolkits" -genes and pathways with lineage-specific variations but deep conservation of function -participate in the behavioral response to social challenge. Here, we studied this toolkit at scale by probing brain transcriptomic responses to social challenge in three distantly related species: honey bees, mice, and three-spined stickleback fish. We aggregated multi-species RNA-seq expression data from specific brain regions and time points after social challenge, achieving spatio-temporal resolution substantially greater than previous work. We conducted sequencing in parallel across species, allowing fair comparison of responses. Because of our complex study design, we developed new comparative analytical methods -including a new cross-species network analysis algorithm. We identified six orthogroups of genes involved in a conserved response to social challenge, including groups represented by Npas4 and Nr4a1, as well as conserved modulation of gene systems such as transcriptional regulators, ion channels, G-protein coupled receptors, and synaptic proteins. We identified two deeply conserved gene modules enriched in mitochondrial fatty acid metabolism and heat shock proteins. Our analysis of this multi-species spatio-temporal expression dataset spanning phyla describes a system wherein nuclear receptors, interacting with chaperones, induce transcriptional changes in mitochondrial activity, neural cytoarchitecture, and synaptic transmission. These data provide support for the hypothesis that core genes and gene sets conserved across animal species have been repeatedly co-opted during evolution of analogous behaviors and may therefore be considered essential toolkits of response to social challenge.peer-reviewed)

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Section: Materials and Methods)mentioning

confidence: 99%

Cross-species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

Saul

Blatti

Yang

et al. 2017

Preprint

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“…Activated LimK1, in turn, phosphorylates and inactivates its target cofilin. Cofilin is a depolymerizing factor and major determinant of dendritic spine structure; cofilin severs the actin filament (F-actin) at its pointed ends (Bamburg and Bernstein, 2010;Mizuno, 2013) and thereby regulates spine morphology, spine motility, and synaptic plasticity (Bosch and Hayashi, 2012;Hotulainen and Hoogenraad, 2010;Lin and Webb, 2009;Pontrello and Ethell, 2009). Growing evidence from studies involving non-neuronal cells indicates that mTORC2 regulates the actin cytoskeleton through Rac1 (Herná ndez-Negrete et al, 2007;Huang et al, 2013).…”

Section: Synapse Elimination and Spine Pruningmentioning

confidence: 99%

A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders

Bagni

Zukin

2019

Neuron

267

258

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Altered synaptic structure and function is a major hallmark of fragile X syndrome (FXS), autism spectrum disorders (ASDs), and other intellectual disabilities (IDs), which are therefore classified as synaptopathies. FXS and ASDs, while clinically and genetically distinct, share significant comorbidity, suggesting that there may be a common molecular and/or cellular basis, presumably at the synapse. In this article, we review brain architecture and synaptic pathways that are dysregulated in FXS and ASDs, including spine architecture, signaling in synaptic plasticity, local protein synthesis, (m)RNA modifications, and degradation. mRNA repression is a powerful mechanism for the regulation of synaptic structure and efficacy. We infer that there is no single pathway that explains most of the etiology and discuss new findings and the implications for future work directed at improving our understanding of the pathogenesis of FXS and related ASDs and the design of therapeutic strategies to ameliorate these disorders. ASDs and FXS: Causes and Clinical Features Approximately 1%-3% of the general population is affected by intellectual disabilities (IDs). IDs are neurodevelopmental disorders defined by significant limitations in intellectual functioning and adaptive behaviors and often exhibit comorbidity with autism (Mefford et al., 2012). Autism spectrum disorders (ASDs) are characterized by high phenotypic heterogeneity, comprising deficits in social interaction and communication as well as repetitive and stereotyped behaviors (

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“…Rho GTPase binding, a process implicated in several aspects of neuronal development as well as neurological diseases 45 and actin binding, a process associated with function and plasticity of dendritic spines and synapses. 46 Module 10 includes genes annotated for adenosine monophosphate deaminase activity and inosine monophosphate biosynthesis, processes associated with purine balance in the brain.…”

Section: Shared Gene Coexpression Modules Responding To Social Chalmentioning

confidence: 99%

Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

Saul

Blatti

Yang

et al. 2018

Genes Brain and Behavior

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Social challenges like territorial intrusions evoke behavioral responses in widely diverging species. Recent work has showed that evolutionary "toolkits"-genes and modules with lineage-specific variations but deep conservation of function-participate in the behavioral response to social challenge. Here, we develop a multispecies computational-experimental approach to characterize such a toolkit at a systems level. Brain transcriptomic responses to social challenge was probed via RNA-seq profiling in three diverged species-honey bees, mice and three-spined stickleback fish-following a common methodology, allowing fair comparisons across species. Data were collected from multiple brain regions and multiple time points after social challenge exposure, achieving anatomical and temporal resolution substantially greater than previous work. We developed statistically rigorous analyses equipped to find homologous functional groups among these species at the levels of individual genes, functional and coexpressed gene modules, and transcription factor subnetworks. We identified six orthogroups involved in response to social challenge, including groups represented by mouse genes Npas4 and Nr4a1, as well as common modulation of systems such as transcriptional regulators, ion channels, G-protein-coupled receptors and synaptic proteins. We also identified conserved coexpression modules enriched for mitochondrial fatty acid metabolism and heat shock that constitute the shared neurogenomic response. Our analysis suggests a toolkit wherein nuclear receptors, interacting with chaperones, induce transcriptional changes in mitochondrial activity, neural cytoarchitecture and synaptic transmission after social challenge. It shows systems-level mechanisms that have been repeatedly co-opted during evolution of analogous behaviors, thus advancing the genetic toolkit concept beyond individual genes.

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Actin and Actin-Binding Proteins: Masters of Dendritic Spine Formation, Morphology, and Function

Cited by 11 publications

References 155 publications

Cross-species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

Cross-species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders

Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

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