Hypoxia alters expression of Zebrafish Microtubule-associated protein Tau (mapta, maptb) gene transcripts

BMC Research Notes

Michael Lardelli¹  Giuseppe Verdile²  Ralph Martins³  Mengqi Chen⁴  Swamynathan Ganesan¹  Morgan Newman¹  Seyyed Hani Moussavi Nik¹ 

[1] Zebrafish Genetics Laboratory, School of Molecular and, Biomedical Sciences, The University of Adelaide, Adelaide SA 5005, Australia;School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia;McCusker Alzheimer’s Disease Research Foundation, Hollywood Private Hospital, Perth, WA, Australia;Centre of Excellence for Alzheimer’s disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia

关键词: Zebrafish;    Hypoxia;    Alzheimer’s disease;    Alternative splicing;    Microtubule-associated protein tau (MAPT);   

Others  :  1125790
DOI  :  10.1186/1756-0500-7-767

 received in 2014-04-29, accepted in 2014-10-14,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Moussavi Nik et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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