Gene nomenclature note: The cation independent mannose-6 phosphate receptor/insulin-like growth factor 2 receptor gene in mammals is symbolized IGF2R with the exception of the mouse that is symbolized Igf2r. In nonmammalian vertebrates the receptor's gene is symbolized igf2r. In this report we use the above gene symbols when referring to mammals, mouse and fish and when we refer to the gene or protein across diverse taxa we use IGF2R or IGF2R, respectively.
Regulation of expression of zebrafish (Danio rerio) insulin-like growth factor 2 receptor: implications for evolution at the IGF2R locus
Article first published online: 10 SEP 2009
© 2009 Wiley Periodicals, Inc.
Evolution & Development
Volume 11, Issue 5, pages 546–558, September/October 2009
How to Cite
Tsalavouta, M., Astudillo, O., Byrnes, L. and Nolan, C. M. (2009), Regulation of expression of zebrafish (Danio rerio) insulin-like growth factor 2 receptor: implications for evolution at the IGF2R locus. Evolution & Development, 11: 546–558. doi: 10.1111/j.1525-142X.2009.00361.x
- Issue published online: 10 SEP 2009
- Article first published online: 10 SEP 2009
SUMMARY The insulin-like growth factor 2 receptor (IGF2R) is an unusual multifunctional receptor that interacts with a diverse variety of ligands. While the receptor has been well-characterized in mammals, little is known of its biology in other vertebrates. In this report, we characterize the expression of the zebrafish (Danio rerio) ortholog of the IGF2R gene. We show that two distinct, cell-type-specific promoters drive transcription of zebrafish igf2r and that these encode receptor isoforms that differ in their amino termini. Both promoters are active in adult fish and during embryonic development, but the proximal promoter generates more abundant transcripts. The 5′-UTR of the more abundantly expressed transcript contains several AUGs upstream of the main start codon, and these negatively regulate translation of a downstream reporter gene. Comparative sequence analysis shows that upstream AUGs (uAUGs) are a feature of IGF2R genes in several other vertebrates, including Xiphophorus, Xenopus, chicken, platypus, and opossum, but not in eutherian mammals. The IGF2R is imprinted in marsupial and placental mammals, and this transcriptional control of receptor abundance was proposed to have evolved following acquisition of an insulin-like growth factor 2 (IGF2) binding site by the ancestral receptor. Our observations suggest that receptor abundance was regulated at translation in ancestral vertebrates, before acquisition of an IGF2 binding site. We propose that evolution of imprinting at the mammalian IGF2R may have facilitated the loss of negative regulation of translation conferred by uAUGs.