Structural and functional characterisation of FOXO/Acan-DAF-16 from the parasitic nematode Angiostrongylus cantonensis.
Fork head box transcription factors subfamily O (FoxO) is regarded to be significant in cell-cycle control, cell differentiation, ageing, stress response, apoptosis, tumour formation and DNA damage repair. In the free-living nematode Caenorhabditis elegans, the FoxO transcription factor is encoded by Ce-daf-16, which is negatively regulated by insulin-like signaling (IIS) and involved in promoting dauer formation through bringing about its hundreds of downstream genes expression. In nematode parasites, orthologues of daf-16 from several species have been identified, with functions in rescue of dauer phenotypes determined in a surrogate system C. elegans. In this study, we identified the FoxO encoding gene, Acan-daf-16, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. Acan-daf-16 encodes two proteins, Acan-DAF-16A and Acan-DAF-16B, consisting of 555 and 491 amino acids, respectively. Both isoforms possess the highly conserved fork head domains. Acan-daf-16A and Acan-daf-16B are expressed from distinct promoters. The expression patterns of Acan-daf-16 isoforms in the C. elegans surrogate system showed that p Acan-daf-16a:gfp was expressed in all cells of C. elegans, including the pharynx, and the expression of p Acan-daf-16b:gfp was restricted to the pharynx. In addition to the same genomic organization to the orthologue in C. elegans, Ce-daf-16, both Acan-DAF-16 isoforms could restore the C. elegans daf-16(mg54) mutation in longevity, dauer formation and stress resistance, in spite of the partial complementation of Acan-DAF-16B isoform in longevity. These findings provide further evidence of the functional conservation of DAF-16s between parasitic nematodes and the free-living nematode C. elegans.
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Baolong
B
Yan
Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Weiwei
W
Sun
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Lanzhu
L
Yan
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Liangliang
L
Zhang
School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Yuan
Y
Zheng
School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Yuzhen
Y
Zeng
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China. Electronic address: hhc@wmu.edu.cn.
Huicong
H
Huang
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China. Electronic address: lsh@wmu.edu.cn.
Shaohui
S
Liang
D000595:Amino Acid Sequence; D017185:Angiostrongylus cantonensis / Q000235:genetics*; D000818:Animals; D018509:DNA, Helminth / Q000737:chemistry; D005260:Female; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid
D018509:DNA, Helminth; D051858:Forkhead Transcription Factors
Angiostrongylus cantonensis; Caenorhabditis elegans; FoxO; Transgenesis; daf-16