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A Novel Member of the Transforming Growth Factor-β (TGF-β) Superfamily from the Filarial NematodesBrugia malayiandB. pahangi

https://doi.org/10.1006/expr.1998.4248Get rights and content

Abstract

Gomez-Escobar, N., Lewis, E., and Maizels, R. M. 1998. A novel member of the transforming growth factor-β (TGF-β) superfamily from the filarial nematodesBrugia malayiandB. pahangi. Experimental Parasitology88, 200–209. Transforming growth factor-β (TGF-β) superfamily genes encode products controlling pattern formation, cell differentiation, and immune-mediated inflammation. Members of this superfamily are known in multicellular organisms from mammals to the model nematodeCaenorhabditis elegans. Using PCR with oligonucleotides complementary to highly conserved motifs in the TGF-β superfamily, we first isolated a genomic clone from the filarial nematodeBrugia malayi. This gene, termed Bm-tgh-1(TGF-β homolog-1), spans 2.5 kb of genomic DNA and contains seven exons. Transcripts of this gene are poorly represented in cDNA libraries, but a full-length cDNA was isolated by RACE fromB. pahangi (Bp-tgh-1). Thetgh-1genes from the two species are >98% identical at the nucleotide and amino acid levels, differing at 18/1576 base pairs and 5/428 amino acids; all nonsynonymous substitutions are in the long N-terminal propeptide. They show a high level of similarity throughout all seven exons to aC. elegansgene on cosmid T25F10. Homology to other members of the TGF-β superfamily is restricted to the C-terminal domain which contains the mature active protein. Key features shared with other members of the superfamily include the tetrabasic proteolytic cleavage site to release an active C-terminal peptide, seven cysteines arrayed in identical fashion, and conserved sequence motifs.tgh-1is most similar to the BMP-1 subfamily involved in developmental signaling in nematodes, insects, and vertebrates. RT-PCR on first-strand cDNA from bothBrugiaspecies, with primers specific to the 3′ end, showed thattgh-1is not expressed in the microfilarial stage, but is detectable in the mosquito-derived infective larvae and is maximal in maturing parasites around the time of molting in the mammalian host. Adult parasites show a relatively low level of expression. The identification oftgh-1, and its preferential expression in developing parasites, suggests that it may be involved in key developmental events in the complex filarial life cycle.

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    To whom correspondence should be addressed. Fax: +44-131-650 5450. E-mail:r.maizels;@ed.ac.uk.

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