Aspp2 negatively regulates body growth but not developmental timing by modulating IRS signaling in zebrafish embryos

Liu, C., Luan, J., Bai, Y., Li, Y., Lu, L., Liu, Y., Hakuno, F., Takahashi, S., Duan, C., and Zhou, J.
General and comparative endocrinology   197: 82-91 (Journal)
Registered Authors
Duan, Cunming, Zhou, Jianfeng
5-bromo-22-deoxyuridine, AO, Acridine orange, Akt, Akt/PKB, Ank, Apoptosis-stimulating protein of p53 2, BrdU, EGFP, Embryonic growth, Erk, HEK, IGF-I receptor, IGF-IR, IGFs, IRS, Insulin receptor substrate, SH3, Src homology 3, Zebrafish, aa, amino acids, ankyrin repeats, enhanced GFP, extracellular signal-regulated kinases, hour post fertilization, hpf, human embryonic kidney, insulin receptor substrate, insulin-like growth factors, protein kinase B
MeSH Terms
  • Adaptor Proteins, Signal Transducing/genetics*
  • Adaptor Proteins, Signal Transducing/metabolism
  • Animals
  • Ankyrins/metabolism
  • Apoptosis/physiology
  • Apoptosis Regulatory Proteins/genetics
  • Body Size/physiology
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental/physiology*
  • HEK293 Cells
  • Humans
  • Insulin/metabolism*
  • Insulin Receptor Substrate Proteins/metabolism*
  • MAP Kinase Signaling System/physiology*
  • Proto-Oncogene Proteins c-akt/metabolism
  • Somatomedins/metabolism
  • Somites/embryology
  • Somites/physiology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • src Homology Domains/physiology
24362258 Full text @ Gen. Comp. Endocrinol.

The growth and developmental rate of developing embryos and fetus are tightly controlled and coordinated to maintain proper body shape and size. The insulin receptor substrate (IRS) proteins, key intracellular transducers of insulin and insulin-like growth factor signaling, play essential roles in the regulation of growth and development. A short isoform of apoptosis-stimulating protein of p53 2 (ASPP2) was recently identified as a binding partner of IRS-1 and IRS-2 in mammalian cells in vitro. However, it is unclear whether ASPP2 plays any role in vertebrate embryonic growth and development. Here, we show that zebrafish Aspp2a and Aspp2b negatively regulate embryonic growth without affecting developmental rate. Human ASPP2 had similar effects on body growth in zebrafish embryos. Aspp2a and 2b inhibit Akt signaling. This inhibition was reversed by coinjection of myr-Akt1, a constitutively active form of Akt1. Zebrafish Aspp2a and Aspp2b physically bound with Irs-1, and the growth inhibitory effects of ASPP2/Aspp2 depend on the presence of their ankyrin repeats and SH3 domains. These findings uncover a novel role of Aspp2 in regulating vertebrate embryonic growth.

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