The membrane palmitoylated protein, MPP6, is involved in myelin formation in the mouse peripheral nervous system

Saitoh, Yurika; Kamijo, Akio; Yamauchi, Junji; Sakamoto, Takeharu; Terada, Nobuo

doi:10.1007/s00418-018-1745-y

Cited by 18 publications

(17 citation statements)

References 51 publications

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“…The biological mechanisms associated with several of the protein products of identified genes have been linked to PTSD pathophysiology in animal and cell models: amygdala-mediated fear extinction [FAM120A ( 38 )], neuronal transcriptional regulation [FOXP2 ( 39 )], brain excitatory/inhibitory balance [ARFGEF2, GABBR1, STAUI1 ( 40 )], intracellular vesicular trafficking and other synaptic activities [ARFGEF2 ( 41 ), MPP6 ( 42 ), SEMA6C ( 43 ), SGCD ( 44 )], and inflammation [HIATL1, TRIM26 ( 45 ), TRIM27 ( 46 ), ZMYM4, ZNF165 ( 47 )]. Blood and brain transcription-wide association and differential gene expression studies of PTSD have also implicated some of these genes, including a blood-based prediction of downregulation of ARFGEF2 in the dorsolateral prefrontal cortex ( 48 ) and a postmortem study of human PTSD cortex indicating downregulation of CTSS expression in the dorsal anterior cingulate cortex and downregulation of OSBPL3 expression in the dorsolateral prefrontal cortex ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Maihofer

Choi

Coleman

et al. 2022

Biological Psychiatry

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Enhancing discovery of genetic variants for PTSD through integration of quantitative phenotypes and trauma exposure information, Biological Psychiatry (2021), doi: https://doi.org/10.1016/ j.biopsych.2021.09.020. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Discussionmentioning

confidence: 99%

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Maihofer

Choi

Coleman

et al. 2022

Biological Psychiatry

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“…2E ), though this was statistically not significant. These four proteins are known to form a tetrameric complex in the membrane cytoskeleton of SLIs [ 31 , 32 ]. The similar relative increase of all four proteins strongly suggests that they are mainly present in a complex in myelin, which is increased in the PNS of Fa2h −/− mice.…”

Section: Resultsmentioning

confidence: 99%

Age-Dependent Increase in Schmidt-Lanterman Incisures and a Cadm4-Associated Membrane Skeletal Complex in Fatty Acid 2-hydroxylase Deficient Mice: a Mouse Model of Spastic Paraplegia SPG35

et al. 2022

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PNS and CNS myelin contain large amounts of galactocerebroside and sulfatide with 2-hydroxylated fatty acids. The underlying hydroxylation reaction is catalyzed by fatty acid 2-hydroxylase (FA2H). Deficiency in this enzyme causes a complicated hereditary spastic paraplegia, SPG35, which is associated with leukodystrophy. Mass spectrometry-based proteomics of purified myelin isolated from sciatic nerves of Fa2h-deficient (Fa2h−/−) mice revealed an increase in the concentration of the three proteins Cadm4, Mpp6 (Pals2), and protein band 4.1G (Epb41l2) in 17-month-old, but not in young (4 to 6-month-old), Fa2h−/− mice. These proteins are known to form a complex, together with the protein Lin7, in Schmidt-Lanterman incisures (SLIs). Accordingly, the number of SLIs was significantly increased in 17-month-old but not 4-month-old Fa2h−/− mice compared to age-matched wild-type mice. On the other hand, the relative increase in the SLI frequency was less pronounced than expected from Cadm4, Lin7, Mpp6 (Pals2), and band 4.1G (Epb41l2) protein levels. This suggests that the latter not only reflect the higher SLI frequency but that the concentration of the Cadm4 containing complex itself is increased in the SLIs or compact myelin of Fa2h−/− mice and may potentially play a role in the pathogenesis of the disease. The proteome data are available via ProteomeXchange with identifier PXD030244.

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“…MPP6 (membrane protein, palmitoylated 6) is a member of the peripheral membraneassociated guanylate kinase (MAGUK). MPP6 interacts with 4.1G, Lin7, and CADM4 proteins in Schwann cells and its KO mice showed hypermyelination of sciatic nerves (Saitoh et al, 2019). A de novo mutation of Mpp6 was reported in an individual with ASD (Iossifov et al, 2014).…”

Section: Btbr/r Degs Are Commonly Altered In Asd Individuals and Animmentioning

confidence: 98%

Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice

Mizuno

Hirota

Ishii

et al. 2020

Front. Cell. Neurosci.

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Mouse line BTBR T+ Iptr3tf/J (hereafter referred as to BTBR/J) is a mouse strain that shows lower sociability compared to the C57BL/6J mouse strain (B6) and thus is often utilized as a model for autism spectrum disorder (ASD). In this study, we utilized another subline, BTBRTF/ArtRbrc (hereafter referred as to BTBR/R), and analyzed the associated brain transcriptome compared to B6 mice using microarray analysis, quantitative RT-PCR analysis, various bioinformatics analyses, and in situ hybridization. We focused on the cerebral cortex and the striatum, both of which are thought to be brain circuits associated with ASD symptoms. The transcriptome profiling identified 1,280 differentially expressed genes (DEGs; 974 downregulated and 306 upregulated genes, including 498 non-coding RNAs [ncRNAs]) in BTBR/R mice compared to B6 mice. Among these DEGs, 53 genes were consistent with ASD-related genes already established. Gene Ontology (GO) enrichment analysis highlighted 78 annotations (GO terms) including DNA/chromatin regulation, transcriptional/translational regulation, intercellular signaling, metabolism, immune signaling, and neurotransmitter/synaptic transmission-related terms. RNA interaction analysis revealed novel RNA–RNA networks, including 227 ASD-related genes. Weighted correlation network analysis highlighted 10 enriched modules including DNA/chromatin regulation, neurotransmitter/synaptic transmission, and transcriptional/translational regulation. Finally, the behavioral analyses showed that, compared to B6 mice, BTBR/R mice have mild but significant deficits in social novelty recognition and repetitive behavior. In addition, the BTBR/R data were comprehensively compared with those reported in the previous studies of human subjects with ASD as well as ASD animal models, including BTBR/J mice. Our results allow us to propose potentially important genes, ncRNAs, and RNA interactions. Analysis of the altered brain transcriptome data of the BTBR/R and BTBR/J sublines can contribute to the understanding of the genetic underpinnings of autism susceptibility.

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The membrane palmitoylated protein, MPP6, is involved in myelin formation in the mouse peripheral nervous system

Cited by 18 publications

References 51 publications

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Age-Dependent Increase in Schmidt-Lanterman Incisures and a Cadm4-Associated Membrane Skeletal Complex in Fatty Acid 2-hydroxylase Deficient Mice: a Mouse Model of Spastic Paraplegia SPG35

Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice

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