PUBLICATION
Hypoxia alters expression of Zebrafish Microtubule-associated protein Tau (mapta, maptb) gene transcripts
- Authors
- Moussavi Nik, S.H., Newman, M., Ganesan, S., Chen, M., Martins, R., Verdile, G., Lardelli, M.
- ID
- ZDB-PUB-141102-6
- Date
- 2014
- Source
- BMC research notes 7: 767 (Journal)
- Registered Authors
- Chen, Mengqi, Lardelli, Michael, Newman, Morgan
- Keywords
- none
- MeSH Terms
-
- Protein Isoforms
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Animals
- Exons
- tau Proteins/genetics*
- tau Proteins/metabolism
- Brain/metabolism*
- Molecular Sequence Data
- Transcription, Genetic*
- Phosphorylation
- Alternative Splicing
- Zebrafish/genetics*
- Zebrafish/metabolism
- In Vitro Techniques
- Cell Hypoxia
- Up-Regulation
- RNA, Messenger/genetics*
- RNA, Messenger/metabolism
- Binding Sites
- Base Sequence
- PubMed
- 25359609 Full text @ BMC Res. Notes
Citation
Moussavi Nik, S.H., Newman, M., Ganesan, S., Chen, M., Martins, R., Verdile, G., Lardelli, M. (2014) Hypoxia alters expression of Zebrafish Microtubule-associated protein Tau (mapta, maptb) gene transcripts. BMC research notes. 7:767.
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.
Conclusion 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping