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 language | English (US) |
|---|---|
| Pages (from-to) | 719-729 |
| Number of pages | 11 |
| Journal | Current Biology |
| Volume | 6 |
| Issue number | 6 |
| State | Published - 1996 |
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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 journal › Article
}
TY - JOUR
T1 - The aimless RasGEF is required for processing of chemotactic signals through G-protein-coupled receptors in Dictyostelium
AU - Insall, Robert H.
AU - Borleis, Jane
AU - Devreotes, Peter N
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0030156329&partnerID=8YFLogxK
M3 - Article
C2 - 8793298
AN - SCOPUS:0030156329
VL - 6
SP - 719
EP - 729
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 6
ER -