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PMID:25143405

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Citation

Cao, X, Yan, J, Shu, S, Brzostowski, JA and Jin, T (2014) Arrestins function in cAR1 GPCR-mediated signaling and cAR1 internalization in the development of Dictyostelium discoideum. Mol. Biol. Cell 25:3210-21

Abstract

Oscillation of chemical signals is a common biological phenomenon, but its regulation is poorly understood. At the aggregation stage of Dictyostelium discoideum development, the chemoattractant cAMP is synthesized and released at 6-min intervals, directing cell migration. Although the G protein-coupled cAMP receptor cAR1 and ERK2 are both implicated in regulating the oscillation, the signaling circuit remains unknown. Here we report that D. discoideum arrestins regulate the frequency of cAMP oscillation and may link cAR1 signaling to oscillatory ERK2 activity. Cells lacking arrestins (adcB(-)C(-)) display cAMP oscillations during the aggregation stage that are twice as frequent as for wild- type cells. The adcB(-)C(-) cells also have a shorter period of transient ERK2 activity and precociously reactivate ERK2 in response to cAMP stimulation. We show that arrestin domain-containing protein C (AdcC) associates with ERK2 and that activation of cAR1 promotes the transient membrane recruitment of AdcC and interaction with cAR1, indicating that arrestins function in cAR1-controlled periodic ERK2 activation and oscillatory cAMP signaling in the aggregation stage of D. discoideum development. In addition, ligand-induced cAR1 internalization is compromised in adcB(-)C(-) cells, suggesting that arrestins are involved in elimination of high-affinity cAR1 receptors from cell surface after the aggregation stage of multicellular development.

Links

PubMed PMC4196870 Online version:10.1091/mbc.E14-03-0834

Keywords

Arrestins/metabolism; Dictyostelium/growth & development; Dictyostelium/metabolism; Mitogen-Activated Protein Kinase 1/metabolism; Phosphorylation; Receptors, Cyclic AMP/metabolism; Receptors, G-Protein-Coupled/metabolism; Signal Transduction/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DICDI:CAR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q55CH0

F

Seeded From UniProt

complete

DICDI:ERK2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q55CH0

F

Seeded From UniProt

complete

DICDI:ADCC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q54QB1

F

Seeded From UniProt

complete

DICDI:ADCC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P13773

F

Seeded From UniProt

complete

DICDI:ADCC

acts_upstream_of_or_within

GO:0002031: G protein-coupled receptor internalization

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q86KB1

P

Seeded From UniProt

complete

DICDI:ADCC

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:ADCC

acts_upstream_of_or_within

GO:0031152: aggregation involved in sorocarp development

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q86KB1

P

Seeded From UniProt

complete

DICDI:ADCC

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:ADCC

acts_upstream_of_or_within

GO:0043405: regulation of MAP kinase activity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q86KB1

P

Seeded From UniProt

complete

DICDI:ADCC

acts_upstream_of_or_within

GO:0106070: regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q86KB1

P

Seeded From UniProt

complete

DICDI:ADCB

acts_upstream_of_or_within

GO:0002031: G protein-coupled receptor internalization

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q55CH0

P

Seeded From UniProt

complete

DICDI:ADCB

acts_upstream_of_or_within

GO:0031152: aggregation involved in sorocarp development

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q55CH0

P

Seeded From UniProt

complete

DICDI:ADCB

acts_upstream_of_or_within

GO:0043405: regulation of MAP kinase activity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q55CH0

P

Seeded From UniProt

complete

DICDI:ADCB

acts_upstream_of_or_within

GO:0106070: regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q55CH0

P

Seeded From UniProt

complete

Notes

See also

References

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