Hypoxia alters expression of Zebrafish Microtubule-associated protein Tau mapta, maptb gene transcriptsReport as inadecuate




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BMC Research Notes

, 7:767

Neuroscience

Abstract

BackgroundMicrotubule-associated protein tau MAPT is abundant in neurons and functions in assembly and stabilization of microtubules to maintain cytoskeletal structure. Human MAPT transcripts undergo alternative splicing to produce 3R and 4R isoforms normally present at approximately equal levels in the adult brain. Imbalance of the 3R-4R isoform ratio can affect microtubule binding and assembly and may promote tau hyperphosphorylation and neurofibrillary tangle formation as seen in neurodegenerative diseases such as frontotemporal dementia FTD and Alzheimer’s disease AD. Conditions involving hypoxia such as cerebral ischemia and stroke can promote similar tau pathology but whether hypoxic conditions cause changes in MAPT isoform formation has not been widely explored. We previously identified two paralogues co-orthologues of MAPT in zebrafish, mapta and maptb.

ResultsIn this study we assess the splicing of transcripts of these genes in adult zebrafish brain under hypoxic conditions. We find hypoxia causes increases in particular mapta and maptb transcript isoforms, particularly the 6R and 4R isoforms of mapta and maptb respectively. Expression of the zebrafish orthologue of human TRA2B, tra2b, that encodes a protein binding to MAPT transcripts and regulating splicing, was reduced under hypoxic conditions, similar to observations in AD brain.

ConclusionOverall, our findings indicate that hypoxia can alter splicing of zebrafish MAPT co-orthologues promoting formation of longer transcripts and possibly generating Mapt proteins more prone to hyperphosphorylation. This supports the use of zebrafish to provide insight into the mechanisms regulating MAPT transcript splicing under conditions that promote neuronal dysfunction and degeneration.

KeywordsMicrotubule-associated protein tau MAPT Alternative splicing Alzheimer’s disease Hypoxia Zebrafish Electronic supplementary materialThe online version of this article doi:10.1186-1756-0500-7-767 contains supplementary material, which is available to authorized users.

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Author: Seyyed Hani Moussavi Nik - Morgan Newman - Swamynathan Ganesan - Mengqi Chen - Ralph Martins - Giuseppe Verdile - Michael 

Source: https://link.springer.com/



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