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

Forbes, Gillian; Schilde, Christina; Lawal, Hajara; Kin, Koryu; Du, Qingyou; Chen, Zhi-hui; Rivero, Francisco; Schaap, Pauline


Gillian Forbes

Christina Schilde

Hajara Lawal

Koryu Kin

Qingyou Du

Zhi-hui Chen

Pauline Schaap


The 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 signaling networks. While genomics has revealed the large size of the GTPase, GEF and GAP repertoire, only a small fraction of their interactions and functions have yet been experimentally explored. Dictyostelid social amoebas have been particularly useful in unraveling 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. Almost completely assembled 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 ancestor. In this work, we identified all GTPases, GEFs and GAP from genomes representative of the four major taxon groups and investigated their phylogenetic relationships and evolutionary conservation and change in their functional domain architecture and in their developmental and cell-type specific expression. We performed hierarchical cluster analysis of the expression profiles of the ~2000 analysed genes to identify putative interacting sets of GTPases, GEFs and GAPs, which highlighted sets known to interact experimentally and many novel combinations. The work represents a valuable resource for research into all fields of cellular regulation.


Forbes, G., Schilde, C., Lawal, H., Kin, K., Du, Q., Chen, Z., …Schaap, P. (in press). Interactome and evolutionary conservation of dictyostelid small GTPases and their direct regulators. Small GTPases,

Journal Article Type Article
Acceptance Date Sep 20, 2021
Online Publication Date Sep 26, 2021
Deposit Date Sep 24, 2021
Publicly Available Date Sep 27, 2022
Journal Small GTPases
Print ISSN 2154-1248
Publisher Taylor & Francis
Peer Reviewed Peer Reviewed
Keywords GTP binding proteins; Guanine nucleotide exchange factors; GTPase activating proteins; Stage- and cell-type specific transcriptomics; Hierarchical clustering; Interactome; Vesicle trafficking; Cell signaling; Cytokinesis; Cell motility
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