Study of the amphioxus IGFBP gene uncovers ancient origin of IGF-independent functions of vertebrate IGFBPs

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 88-108-GHRH, GH & IGF Biology & Signaling
Basic/Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-103
Jianfeng Zhou1, Jianhai Xiang2, Shicui Zhang3 and Cunming Duan*4
1Ocean University of China, Qingdao, 2Chinese Academy of Sciences, 3Ocean University of China, 4Univ of Michigan, Ann Arbor, MI
Insulin-like growth factors (IGFs) play key roles in regulating vertebrate development, growth, reproduction, and aging. In extracellular fluids, IGFs are bound and regulated by a family of IGF binding proteins (IGFBPs). While all known IGFBPs are secreted proteins, some are also found in the nucleus and possess IGF-independent activities. When and how these distinct modes of biological actions have evolved is unknown.  In this study, we identified and analysed an IGFBP from amphioxus. Amphioxus is the closest living relative of the modern vertebrates. The amphioxus IGFBP shares all major structural characteristics of vertebrate IGFBPs. Phylogenetic analyses place it in a basal position in the IGFBP lineage. Ligand blot analysis reveals that amphioxus IGFBP does not bind to IGF-I or II. Changing its Phe70 into Leu, however, is sufficient to convert it into a functional IGF binder. When tested in cultured cells, amphioxus IGFBP is found in the nucleus and this is attributed to two redundant nuclear localization sequences in the L-domain. Furthermore, its N-terminal domain has strong transactivation activity. Forced expression of amphioxus IGFBP in zebrafish embryos results in dorsalized phenotypes. This action requires the nuclear localization. These results suggest that the nuclear localization and transcriptional activity of IGFBPs are ancient functions and the IGF binding function may have been acquired by opportunistic gain-of-functional mutations later in evolution.

Nothing to Disclose: JZ, JX, SZ, CD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by NSF Grant IOS-1051034