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Functional and molecular features of the calmodulin-interacting protein IQCG required for haematopoiesis in zebrafish

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  • Li-Ting Chen

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine
    Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and SITU School of Medicine)

  • Wen-Xue Liang

    (Central Laboratory, Lianyungang First People’s Hospital)

  • Shuo Chen

    (Ludwig Institute for Cancer Research, Old Road Campus Research Building, University of Oxford)

  • Ren-Ke Li

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine
    Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and SITU School of Medicine)

  • Jue-Ling Tan

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine)

  • Peng-Fei Xu

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine)

  • Liu-Fei Luo

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine)

  • Lei Wang

    (Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and SITU School of Medicine)

  • Shan-He Yu

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine)

  • Guoyu Meng

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine)

  • Keqin Kathy Li

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine)

  • Ting-Xi Liu

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine)

  • Zhu Chen

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine)

  • Sai-Juan Chen

    (State Key Laboratory of Medical Genomics and Shanghai, Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University (SITU) School of Medicine
    Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and SITU School of Medicine)

Abstract

We previously reported a fusion protein NUP98–IQCG in an acute leukaemia, which functions as an aberrant regulator of transcriptional expression, yet the structure and function of IQCG have not been characterized. Here we use zebrafish to investigate the role of iqcg in haematopoietic development, and find that the numbers of haematopoietic stem cells and multilineage-differentiated cells are reduced in iqcg-deficient embryos. Mechanistically, IQCG binds to calmodulin (CaM) and acts as a molecule upstream of CaM-dependent kinase IV (CaMKIV). Crystal structures of complexes between CaM and IQ domain of IQCG reveal dual CaM-binding footprints in this motif, and provide a structural basis for a higher CaM–IQCG affinity when deprived of calcium. The results collectively allow us to understand IQCG-mediated calcium signalling in haematopoiesis, and propose a model in which IQCG stores CaM at low cytoplasmic calcium concentrations, and releases CaM to activate CaMKIV when calcium level rises.

Suggested Citation

  • Li-Ting Chen & Wen-Xue Liang & Shuo Chen & Ren-Ke Li & Jue-Ling Tan & Peng-Fei Xu & Liu-Fei Luo & Lei Wang & Shan-He Yu & Guoyu Meng & Keqin Kathy Li & Ting-Xi Liu & Zhu Chen & Sai-Juan Chen, 2014. "Functional and molecular features of the calmodulin-interacting protein IQCG required for haematopoiesis in zebrafish," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4811
    DOI: 10.1038/ncomms4811
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    Cited by:

    1. Annie M Westerlund & Lucie Delemotte, 2018. "Effect of Ca2+ on the promiscuous target-protein binding of calmodulin," PLOS Computational Biology, Public Library of Science, vol. 14(4), pages 1-27, April.

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