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Switching of chemoattractant receptors programs development and morphogenesis in Dictyostelium: receptor subtypes
J Y Kim1, J A Borleis, P N Devreotes
1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Abstract:
One of the common functional features among G-protein coupled receptors is the occurrence of multiple subtypes involved in similar signal transduction events. The cAMP chemoattractant receptor family of Dictyostelium discoideum is composed of four receptors (cAR1-cAR4), which are expressed sequentially throughout the developmental transition from a unicellular to a multicellular organism. The receptors differ in affinity for cAMP and in the sequences of their C-terminal domains. In this study, we constitutively expressed cAR1, cAR2, and cAR3 as well as a series of chimeric and mutant receptors and assessed the capacity of each to mediate chemotaxis, activation of adenylyl cyclase and actin polymerization, and rescue the developmental defect of car1-/car3- cells. We found that various receptors and mutants sense different concentration ranges of cAMP but all can mediate identical responses during the aggregation stage of development. The responses displayed very similar kinetics, suggesting no major differences in regulatory properties attributable to the C-terminal domains. We speculate that switching of receptor subtypes during development enables the organism to respond to the changing concentrations of the chemoattractant and thereby program morphogenesis appropriately.
Insights
Dictyostelium discoideum uses multiple cAMP chemoattractant receptors (cARs) sequentially during development. Despite differing cAMP affinities, these receptors mediate similar chemotaxis and developmental responses.
Area of Science:
- Cellular and Molecular Biology
- Developmental Biology
- Biochemistry
Background:
- G-protein coupled receptors often feature multiple subtypes for signal transduction.
- The Dictyostelium discoideum cAMP chemoattractant receptor (cAR) family includes four receptors (cAR1-cAR4) expressed sequentially during development.
- These receptors exhibit variations in cAMP affinity and C-terminal domain sequences.
Purpose of the Study:
- To investigate the functional roles of cAR1, cAR2, and cAR3 in Dictyostelium discoideum development.
- To determine how differences in receptor subtypes and C-terminal domains affect chemotaxis, signal transduction, and developmental rescue.
- To understand the contribution of distinct cARs to sensing varying chemoattractant concentrations during morphogenesis.
Main Methods:
- Constitutive expression of cAR1, cAR2, and cAR3.
- Creation and assessment of chimeric and mutant receptors.
- Evaluation of chemotaxis, adenylyl cyclase activation, and actin polymerization.
- Testing the rescue of developmental defects in car1-/car3- mutant cells.
Main Results:
- Different cAR variants sense distinct cAMP concentration ranges.
- All tested receptors and mutants mediated identical responses during the aggregation stage.
- Response kinetics were similar across variants, indicating conserved regulatory properties.
- C-terminal domains did not appear to significantly alter regulatory properties.
Conclusions:
- Dictyostelium discoideum receptor subtypes can mediate similar developmental responses despite varying cAMP affinities.
- The sequential expression of cARs likely allows the organism to adapt to changing chemoattractant levels.
- This adaptation mechanism is crucial for programming appropriate morphogenesis during development.