title: Hypoxia alters expression of zebrafish microtubule-associated protein tau (mapta, maptb) gene transcripts.
abstract: BACKGROUND
  Microtubule-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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Overall, 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.
authors.affiliation: Discipline of Genetics, School of Molecular and Biomedical Sciences, The University of Adelaide, SA 5005 Adelaide, Australia. seyyed.moussavinik@adelaide.edu.au.
authors.forename: Seyyed Hani
authors.initials: SH
authors.lastname: Moussavi Nik
authors.forename: Morgan
authors.initials: M
authors.lastname: Newman
authors.forename: Swamynathan
authors.initials: S
authors.lastname: Ganesan
authors.forename: Mengqi
authors.initials: M
authors.lastname: Chen
authors.forename: Ralph
authors.initials: R
authors.lastname: Martins
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Verdile
authors.forename: Michael
authors.initials: M
authors.lastname: Lardelli
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D015687:Cell Hypoxia; D005091:Exons; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C000598882:Mapta protein, zebrafish; D020033:Protein Isoforms; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D016875:tau Proteins