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Cartas Cejudo, Paz

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https://academica-e.unavarra.es/handle/2454/51533

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Cartas Cejudo

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Paz

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Ciencias de la Salud

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0000-0002-6182-7445

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812658

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Subject: Synapse × Subject: Cytoskeleton ×

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    PublicationOpen Access
    Deregulated transcription and proteostasis in adult mapt knockout mouse
    (MDPI, 2023) Andrés Benito, Pol; Flores, África; Busquet-Areny, Sara; Carmona, Margarita; Ausín, Karina; Cartas Cejudo, Paz; Lachén Montes, Mercedes; Río, José Antonio del; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Ferrer, Isidro; Ciencias de la Salud; Osasun Zientziak
    Transcriptomics and phosphoproteomics were carried out in the cerebral cortex of B6.Cg-Mapttm1(EGFP)Klt (tau knockout: tau-KO) and wild-type (WT) 12 month-old mice to learn about the effects of tau ablation. Compared with WT mice, tau-KO mice displayed reduced anxiety-like behavior and lower fear expression induced by aversive conditioning, whereas recognition memory remained unaltered. Cortical transcriptomic analysis revealed 69 downregulated and 105 upregulated genes in tau-KO mice, corresponding to synaptic structures, neuron cytoskeleton and transport, and extracellular matrix components. RT-qPCR validated increased mRNA levels of col6a4, gabrq, gad1, grm5, grip2, map2, rab8a, tubb3, wnt16, and an absence of map1a in tau-KO mice compared with WT mice. A few proteins were assessed with Western blotting to compare mRNA expression with corresponding protein levels. Map1a mRNA and protein levels decreased. However, ¿-tubulin III and GAD1 protein levels were reduced in tau-KO mice. Cortical phosphoproteomics revealed 121 hypophosphorylated and 98 hyperphosphorylated proteins in tau-KO mice. Deregulated phosphoproteins were categorized into cytoskeletal (n = 45) and membrane proteins, including proteins of the synapses and vesicles, myelin proteins, and proteins linked to membrane transport and ion channels (n = 84), proteins related to DNA and RNA metabolism (n = 36), proteins connected to the ubiquitin-proteasome system (UPS) (n = 7), proteins with kinase or phosphatase activity (n = 21), and 22 other proteins related to variegated pathways such as metabolic pathways, growth factors, or mitochondrial function or structure. The present observations reveal a complex altered brain transcriptome and phosphoproteome in tau-KO mice with only mild behavioral alterations.