Interactome and evolutionary conservation of Dictyostelid small GTPases and their direct regulators

Gillian Forbes, Christina Schilde, Hajara Lawal, Koryu Kin, Qingyou Du, Zhi-Hui Chen, Francisco Rivero, Pauline Schaap (Lead / Corresponding author)

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Abstract

GTP binding proteins known as small GTPases make up one of the largest groups of regulatory proteins and control almost all functions of living cells. Their activity is under, respectively, positive and negative regulation by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), which together with their upstream regulators and the downstream targets of the small GTPases form formidable signalling networks. While genomics has revealed the large size of the GTPase, GEF and GAP repertoires, only a small fraction of their interactions and functions have yet to be experimentally explored. Dictyostelid social amoebas have been particularly useful in unravelling the roles of many proteins in the Rac-Rho and Ras-Rap families of GTPases in directional cell migration and regulation of the actin cytoskeleton. Genomes and cell-type specific and developmental transcriptomes are available for Dictyostelium species that span the 0.5 billion years of evolution of the group from their unicellular ancestors. In this work, we identified all GTPases, GEFs and GAPs from genomes representative of the four major taxon groups and investigated their phylogenetic relationships and evolutionary conservation and changes in their functional domain architecture and in their developmental and cell-type specific expression. We performed a hierarchical cluster analysis of the expression profiles of the ~2000 analysed genes to identify putative interacting sets of GTPases, GEFs and GAPs, which highlight sets known to interact experimentally and many novel combinations. This work represents a valuable resource for research into all fields of cellular regulation.

Original languageEnglish
Pages (from-to)239-254
Number of pages16
JournalSmall GTPases
Volume13
Issue number1
Early online date5 Oct 2021
DOIs
Publication statusE-pub ahead of print - 5 Oct 2021

Keywords

  • GTP binding proteins
  • GTPase activating proteins
  • cell motility
  • cell signalling
  • cytokinesis
  • guanine nucleotide exchange factors
  • hierarchical clustering
  • interactome
  • stage- and cell-type specific transcriptomics
  • vesicle trafficking

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