PUBLICATION

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

Authors
Chen, L.T., Liang, W.X., Chen, S., Li, R.K., Tan, J.L., Xu, P.F., Luo, L.F., Wang, L., Yu, S.H., Meng, G., Li, K.K., Liu, T.X., Chen, Z., Chen, S.J.
ID
ZDB-PUB-140513-54
Date
2014
Source
Nature communications   5: 3811 (Journal)
Registered Authors
Chen, Zhu, Liu, Ting Xi, Xu, Peng-Fei
Keywords
none
MeSH Terms
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4/metabolism
  • Calmodulin/metabolism*
  • Cell Proliferation
  • Gene Knockdown Techniques
  • HSP70 Heat-Shock Proteins/metabolism
  • Hematopoiesis
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
24787902 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes