A G alpha-Stimulated RapGEF Is a Receptor-Proximal Regulator of Dictyostelium Chemotaxis

Liu Y., Lacal J., Veltman D. M. , Fusetti F., van Haastert P. J. M. , Firtel R. A. , ...More

DEVELOPMENTAL CELL, vol.37, no.5, pp.458-472, 2016 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 5
  • Publication Date: 2016
  • Doi Number: 10.1016/j.devcel.2016.05.001
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.458-472


Chemotaxis, or directional movement toward extracellular chemical gradients, is an important property of cells that is mediated through G-protein-coupled receptors (GPCRs). Although many chemotaxis pathways downstream of G beta gamma have been identified, few G alpha effectors are known. G alpha effectors are of particular importance because they allow the cell to distinguish signals downstream of distinct chemoattractant GPCRs. Here we identify GflB, a G alpha 2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1. GflB localizes to the leading edge and functions as a G alpha-stimulated, Rap1-specific guanine nucleotide exchange factor required to balance Ras and Rap signaling. The kinetics of GflB translocation are fine-tuned by GSK-3 phosphorylation. Cells lacking GflB display impaired Rap1/Ras signaling and actin and myosin dynamics, resulting in defective chemotaxis. Our observations demonstrate that GflB is an essential upstream regulator of chemoattractant-mediated cell polarity and cytoskeletal reorganization functioning to directly link G alpha activation to monomeric G-protein signaling.