Myotubularin-related protein protects against neuronal degeneration mediated by oxidative stress or infection

Kaur, Supender; Sang, Yu; Aballay, Alejandro

doi:10.1016/j.jbc.2022.101614

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…SEPHS1 influences selenium metabolism pathways, deficiencies in which lead to oxidative stress [57] and increased inflammation and degradation of extracellular matrix [58]. MTMR10 plays a role in the extracellular matrix, including in neurons and protects dendrites in response to oxidative stress [59]; their interaction may relate to regulation of inflammation and stress response.…”

Section: Twis Associations-empirical Resultsmentioning

confidence: 99%

Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits

et al. 2023

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It remains unknown to what extent gene-gene interactions contribute to complex traits. Here, we introduce a new approach using predicted gene expression to perform exhaustive transcriptome-wide interaction studies (TWISs) for multiple traits across all pairs of genes expressed in several tissue types. Using imputed transcriptomes, we simultaneously reduce the computational challenge and improve interpretability and statistical power. We discover (in the UK Biobank) and replicate (in independent cohorts) several interaction associations, and find several hub genes with numerous interactions. We also demonstrate that TWIS can identify novel associated genes because genes with many or strong interactions have smaller single-locus model effect sizes. Finally, we develop a method to test gene set enrichment of TWIS associations (E-TWIS), finding numerous pathways and networks enriched in interaction associations. Epistasis is may be widespread, and our procedure represents a tractable framework for beginning to explore gene interactions and identify novel genomic targets.

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Section: Twis Associations-empirical Resultsmentioning

confidence: 99%

Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits

et al. 2023

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“…SEPHS1 influences selenium metabolism pathways, deficiencies in which lead to oxidative stress 48 and increased inflammation and degradation of extracellular matrix 49 . MTMR10 plays a role in the extracellular matrix, including in neurons and protects dendrites in response to oxidative stress 50 ; their interaction may relate to regulation of inflammation and stress response. SC was associated (final meta-analysis p =3.71e-10, discovery p <5e-9, replication p =0.023) with an interaction between CCNE1 , a cyclin family protein required for CDK kinase activity, and SF3B1 , a component of the splicosome 51 , which may highlight the role of transcription regulation and modification with circadian cycles and the relationships of smoking cessation with sleep chronicity 52 and disturbance 53 .…”

Section: Resultsmentioning

confidence: 99%

Transcriptome-Wide Gene-Gene Interaction Association Study Elucidates Pathways and Functional Enrichment of Complex Traits

Evans

Arehart

Grotzinger

et al. 2022

Preprint

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It remains unknown to what extent gene-gene interactions contribute to complex traits. Here, we introduce a new approach using predicted gene expression to perform exhaustive transcriptome-wide interaction studies (TWISs) for multiple traits across all pairs of genes expressed in several tissue types. Using imputed transcriptomes, we simultaneously reduce the computational challenge and improve interpretability and statistical power. We discover and replicate several interaction associations, and find several hub genes with numerous interactions. We also demonstrate that TWIS can identify novel associated genes because genes with many or strong interactions have smaller single-locus model effect sizes. Finally, we develop a method to test gene set enrichment of TWIS associations (E-TWIS), finding numerous pathways and networks enriched in interaction associations. Epistasis is likely widespread, and our procedure represents a tractable framework for beginning to explore gene interactions and identify novel genomic targets.

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“…Changes in dendrite morphology are also observed in amphid AWC neurons upon exposure to bacterial pathogens such as Pseudomonas aeruginosa , a phenomenon that has also been used as a model of neurodegeneration ( Wu et al . 2015 ; Kaur and Aballay 2020 ; Kaur et al . 2022 ).…”

Section: Ciliated Dendrites Not Ensheathed By Gliamentioning

confidence: 99%

Dendrite morphogenesis in Caenorhabditis elegans

Heiman,

Bülow

2024

Genetics

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Since the days of Ramón y Cajal, the vast diversity of neuronal and particularly dendrite morphology has been used to catalog neurons into different classes. Dendrite morphology varies greatly and reflects the different functions performed by different types of neurons. Significant progress has been made in our understanding of how dendrites form and the molecular factors and forces that shape these often elaborately sculpted structures. Here, we review work in the nematode Caenorhabditis elegans that has shed light on the developmental mechanisms that mediate dendrite morphogenesis with a focus on studies investigating ciliated sensory neurons and the highly elaborated dendritic trees of somatosensory neurons. These studies, which combine time-lapse imaging, genetics, and biochemistry, reveal an intricate network of factors that function both intrinsically in dendrites and extrinsically from surrounding tissues. Therefore, dendrite morphogenesis is the result of multiple tissue interactions, which ultimately determine the shape of dendritic arbors.

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Myotubularin-related protein protects against neuronal degeneration mediated by oxidative stress or infection

Cited by 5 publications

References 49 publications

Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits

Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits

Transcriptome-Wide Gene-Gene Interaction Association Study Elucidates Pathways and Functional Enrichment of Complex Traits

Dendrite morphogenesis in Caenorhabditis elegans

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