A shortcut from GPCR signaling to Rac-mediated actin cytoskeleton through an ELMO/DOCK complex.
Chemotaxis, chemoattractant-guided directional cell migration, plays major roles in human innate immunity and in development of a model organism Dictyostelium discoideum. Human leukocytes and D. disscoideum share remarkable similarities in the molecular mechanisms that control chemotaxis. These cells use G-Protein-Coupled Receptors (GPCRs), such as chemokine receptors, to control a signaling network that carries out chemotactic gradient sensing and directs cell migration. Diverse chemokines bind to their receptors to activate small G protein Rac through an evolutionarily conserved mechanism. Elmo and Dock180 proteins form ELMO/Dock180 complexes functioning as guanine nucleotide exchange factors (GEFs) for Rac activation. However, the linkage between GPCR to Elmo/Dock180 for Rac activation that controls F-actin dynamics remained unclear. Recently, we discovered a novel function of an ELMO protein in Dictyostelium discoideum linking GPCR signaling from Gβ to actin dynamics through regulating Rac activation during chemotaxis.
Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA. xxu@niaid.nih.gov
Xuehua
X
Xu
Tian
T
Jin
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002633:Chemotaxis; D003599:Cytoskeleton / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015800:Protozoan Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015800:Protozoan Proteins; D043562:Receptors, G-Protein-Coupled; D020744:rac GTP-Binding Proteins