Analyzing the role of the Ras effector TJ1 in controlling chemotaxis in Dictyostelium discoideum
Zusammenfassung der Projektergebnisse
Chemotaxis plays a central role in various biological processes such as cellular morphogenesis, innate immunity, inflammation, and metastasis of cancer cells. During chemotaxis in Dictyostelium, cells respond to shallow extracellular gradients, which become highly amplified intracellularly via the localized activation of Ras and PI3K resulting in F-actin polymerization and pseudopod formation in the direction of the chemoattractant source. TJ1, a member of the MRL (Mig10/RIAM/Lpd) family of adaptor proteins, is a putative Ras effector that might signal to the actin cytoskeleton. Deletion of the RA domains leads to a decrease in speed and directionality during chemotaxis and deletion of both CH domains, which often function as actin binding domains, leads to pseudopodsplitting, a phenotype previously observed in mutants for members of the SCAR/WAVE complex. TJ1 might function through the interaction with the PKB-related kinase PKBR1, since TJ1 can interact with PKBR1. For TJ1 to be fully functional, phosphorylation at Serine 861 by GSK3 is required. The loss of TJ1 leads to aggregation defects: tj1 null cells exhibit greatly reduced speed and polarity compared to wild-type cells during migration towards a chemoattractant source, show defects in the directionality of their movement, and exhibit an increased number of lateral pseudopodia. Further experimentation will be necessary to place TJ1 in the network of known players during Dictyostelium chemotaxis.
Projektbezogene Publikationen (Auswahl)
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The regulation of cell motility and chemotaxis by phospholipid signaling. J Cell Sci. 2008 Mar 1;121(Pt 5):551-9
Kölsch V, Charest PG, Firtel RA
