Caenorhabditus elegans arrestin regulates neural G protein signaling and olfactory adaptation and recovery.
Although regulation of G protein-coupled receptor signaling by receptor kinases and arrestins is a well established biochemical process, the physiological significance of such regulation remains poorly understood. To better understand the in vivo consequences of arrestin function, we have examined the function of the sole arrestin in Caenorhabditis elegans (ARR-1). ARR-1 is primarily expressed in the nervous system, including the HSN neuron and various chemosensory neurons involved in detecting soluble and volatile odorants. arr-1 null mutants exhibit normal chemotaxis but have significant defects in olfactory adaptation and recovery to volatile odorants. In contrast, adaptation is enhanced in animals overexpressing ARR-1. Both the adaptation and recovery defects of arr-1 mutants are rescued by transgenic expression of wild-type ARR-1, whereas expression of a C-terminally truncated ARR-1 effectively rescues only the adaptation defect. A potential mechanistic basis for these findings is revealed by in vitro studies demonstrating that wild-type ARR-1 binds proteins of the endocytic machinery and promotes receptor endocytosis, whereas C-terminally truncated ARR-1 does not. These results demonstrate that ARR-1 functions to regulate chemosensory signaling, enabling organisms to adapt to a variety of environmental cues, and provide an in vivo link between arrestin, receptor endocytosis, and temporal recovery from adaptation.
Palmitessa
Aimee
A
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Hess
Heather A
HA
Bany
I Amy
IA
Kim
You-Me
YM
Koelle
Michael R
MR
Benovic
Jeffrey L
JL
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D019393:Arrestin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001547:Benzaldehydes / Q000737:chemistry; D015152:Blotting, Northern; D019556:COS Cells; D017173:Caenorhabditis elegans; D002460:Cell Line; D002478:Cells, Cultured; D002633:Chemotaxis; D002966:Clathrin / Q000378:metabolism; D003931:Diacetyl / Q000737:chemistry; D004705:Endocytosis; D005091:Exons; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D009812:Odorants; D009833:Olfactory Pathways / Q000378:metabolism*; D000439:Pentanols / Q000737:chemistry; D010641:Phenotype; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013997:Time Factors
D019393:Arrestin; D001547:Benzaldehydes; D002966:Clathrin; D000439:Pentanols; D049452:Green Fluorescent Proteins; C029683:isopentyl alcohol; D019204:GTP-Binding Proteins; D003931:Diacetyl; C032175:benzaldehyde