The aimless RasGEF is required for processing of chemotactic signals through G-protein-coupled receptors in Dictyostelium

Robert H. Insall, Jane Borleis, Peter N Devreotes

Research output: Contribution to journalArticle

Abstract

Background: Ras proteins are small GTP-binding proteins that play an essential role in a wide range of processes, particularly in mammalian growth control. They act as molecular switches, being inactive when GDP is bound, and active when associated with GTP. Activation is accomplished by guanine nucleotide exchange factors (RasGEFs); when RasGEFs interact with Ras proteins, GDP is allowed to escape, and is replaced by GTP. Dictyostelium responds to chemoattractants through typical seven transmembrane domain receptors and heterotrimeric G proteins. There are at least five different Dictyostelium Ras genes, whose functions are not yet known. Results: We have isolated the aimless gene, which encodes the Dictyostelium homologue of RasGEFs, during a screen for insertional mutants that fail to aggregate. We found that aimless null mutants grew at a normal rate, but were severely impaired in both chemotaxis and activation of adenylyl cyclase, both of which are critical for the early stages of development. Although coupling between receptors and their G proteins is unaffected, and several cyclic AMP (cAMP)-mediated responses appear normal, activation of adenylyl cyclase by receptors and GTPγS (a non-hydrolyzable GTP analogue) is reduced by up to 95 %. The motility of mutant cells appears normal, suggesting a true defect in gradient sensing. Conclusions: The discovery of the aimless gene adds an interesting new member to the family of RasGEFs. Our data suggest an unforeseen role for a RasGEF, and therefore presumably a complete Ras pathway, in the processing of chemotactic signals through G-protein-coupled receptors.

Original languageEnglish (US)
Pages (from-to)719-729
Number of pages11
JournalCurrent Biology
Volume6
Issue number6
StatePublished - 1996

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Dictyostelium
G-Protein-Coupled Receptors
Guanosine Triphosphate
G-proteins
ras Proteins
adenylate cyclase
Genes
Chemical activation
GTP-Binding Proteins
Adenylyl Cyclases
mutants
receptors
Processing
Guanine Nucleotide Exchange Factors
Heterotrimeric GTP-Binding Proteins
chemoattractants
ras Genes
genes
Chemotactic Factors
chemotaxis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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The aimless RasGEF is required for processing of chemotactic signals through G-protein-coupled receptors in Dictyostelium. / Insall, Robert H.; Borleis, Jane; Devreotes, Peter N.

In: Current Biology, Vol. 6, No. 6, 1996, p. 719-729.

Research output: Contribution to journalArticle

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