CNP-1 (ARRD-17), a Novel Substrate of Calcineurin, Is Critical for Modulation of Egg-Laying and Locomotion in Response to Food and Lysine Sensation in Caenorhabditis elegans

Jee, Chang Hoon; Choi, Tae Woo; Kalichamy, Karunambigai; Yee, Jong Zin; Song, Hyun Ok; Ji, Yon Ju; Lee, Jungsoo; Lee, Jin I.; L’Étoile, Noëlle D.; Ahnn, Joohong; Lee, Sun Kyung

doi:10.1016/j.jmb.2012.01.012

Cited by 17 publications

(12 citation statements)

References 45 publications

(52 reference statements)

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“…[20], [32], [42], [43], [44] Others have reported that the mammalian aArrs TXNIP and Arrdc1 are ubiquitinated dependent on their PY motifs, and that this results in their degradation. [24], [45], [46], [47] Use of Phosphosite mining [48] revealed mass spectroscopy evidence of TXNIP ubiquitination at 16 different lysine residues (8 of those were identified in 5 or more studies) and of ARRDC4 ubiquitination from one in vivo proteomic survey of ubiquitination (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mammalian Alpha Arrestins Link Activated Seven Transmembrane Receptors to Nedd4 Family E3 Ubiquitin Ligases and Interact with Beta Arrestins

Shea

Rowell

et al. 2012

PLoS ONE

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The complement of fungal cell surface proteins is widely regulated by ubiquitination of membrane proteins, which results in their endocytosis and vacuolar degradation. For diverse fungal transporters, the specificity of ubiquitination is conferred by alpha arrestin adaptors, which recruit the Nedd4 family E3 ubiquitin ligase Rsp5. A recent study showed that one mammalian alpha arrestin also mediates ubiquitination and lysosomal trafficking of an activated plasma membrane receptor. Here we first screen all five widely-expressed human alpha arrestins for subcellular localization in ligand-stimulated and -unstimulated cells overexpressing the seven transmembrane receptor vasopressin 2. We then characterize the effects of alpha arrestins ARRDC3 and ARRDC4 upon activation of the seven transmembrane receptors vasopressin 2 and beta adrenergic 2. Using biochemical and imaging approaches, we show that ligand-activated receptors interact with alpha arrestins, and this results in recruitment of Nedd4 family E3 ubiquitin ligases and receptor ubiquitination – which are known to result in lysosomal trafficking. Our time course studies show these effects occur in the first 1–5 minutes after ligand activation, the same time that beta arrestins are known to have roles in receptor endocytic trafficking and kinase signaling. We tested the possibility that alpha and beta arrestins function coordinately and found co-immunoprecipitation and colocalization evidence to support this. Others recently reported that Arrdc3 knockout mice are lean and resistant to obesity. In the course of breeding our own Arrdc3-deficient mice, we observed two novel phenotypes in homozygotes: skin abnormalities, and embryonic lethality on normal chow diet, but not on high fat diet. Our findings suggest that alpha and beta arrestins function coordinately to maintain the optimal complement and function of cell surface proteins according to cellular physiological context and external signals. We discuss the implications of the alpha arrestin functions in fungi having evolved into coordinated alpha/beta arrestin functions in animals.

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Section: Resultsmentioning

confidence: 99%

Mammalian Alpha Arrestins Link Activated Seven Transmembrane Receptors to Nedd4 Family E3 Ubiquitin Ligases and Interact with Beta Arrestins

Shea

Rowell

et al. 2012

PLoS ONE

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“…Conserved Interaction of Calcineurin with ␣-Arrestins and Its Implications-A Caenorhabditis elegans ␣-arrestin, CNP-1/ ArrD-17, interacts with the catalytic subunit of calcineurin and is a calcineurin substrate in vitro (57). Although no calcineurindocking site was identified in the nematode protein, we note that CNP-1/ArrD-17 contains near its C terminus a variant PXIXIT motif (PIVIGS) that is conserved in its mammalian ␣-arrestin relatives ARRDC2-4 and TNXIP (as PLVIGS or PLVIGT).…”

Section: Discussionmentioning

confidence: 99%

“…Mediates Its Association with Calcineurin-Yeast two-hybrid analysis successfully identified several calcineurin substrates (43,45,57,58). To identify additional potential substrates, we conducted a yeast two-hybrid screen using a Gal4-DBD fusion to Cna1, a catalytic subunit of calcineurin, as the bait.…”

Section: C-terminal Pxixit Motif In Aly1mentioning

confidence: 99%

A Calcineurin-dependent Switch Controls the Trafficking Function of α-Arrestin Aly1/Art6

O’Donnell

Huang

Thorner

et al. 2013

Journal of Biological Chemistry

103

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Background:In response to nutrient signals, ␣-arrestins selectively regulate trafficking of membrane transporters. Results: Aly1 is a substrate of the phosphatase calcineurin, and dephosphorylation triggers Aly1-dependent internalization of the permease Dip5. Conclusion: Endocytic function of ␣-arrestins is stimulated by removal of inhibitory phosphorylation. Significance: These insights define a molecular mechanism controlling the function of an ␣-arrestin in endocytosis, which is critical for cellular adaptation.

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“…Along with Aly1 (78), Rod1 is now the second yeast ␣-arrestin shown to be under CN regulation. Also, in Caenorhabditis elegans, the function of ␣-arrestin CNP-1/ArrD-17 requires CN-mediated dephosphorylation (136), suggesting that CN control of ␣-arrestin dephosphorylation is a conserved regulatory mechanism.…”

Section: Figmentioning

confidence: 99%

Specific α-Arrestins Negatively Regulate Saccharomyces cerevisiae Pheromone Response by Down-Modulating the G-Protein-Coupled Receptor Ste2

Alvaro

O’Donnell

Prosser

et al. 2014

Molecular and Cellular Biology

159

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e G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate responses to extracellular stimuli by mediating ligand-dependent activation of cognate heterotrimeric G proteins. In yeast, occupancy of GPCR Ste2 by peptide pheromone ␣-factor initiates signaling by releasing a stimulatory G␤␥ complex (Ste4-Ste18) from its inhibitory G␣ subunit (Gpa1). Prolonged pathway stimulation is detrimental, and feedback mechanisms have evolved that act at the receptor level to limit the duration of signaling and stimulate recovery from pheromone-induced G 1 arrest, including upregulation of the expression of an ␣-factor-degrading protease (Bar1), a regulator of G-protein signaling protein (Sst2) that stimulates Gpa1-GTP hydrolysis, and Gpa1 itself. Ste2 is also downregulated by endocytosis, both constitutive and ligand induced. Ste2 internalization requires its phosphorylation and subsequent ubiquitinylation by membrane-localized protein kinases (Yck1 and Yck2) and a ubiquitin ligase (Rsp5). Here, we demonstrate that three different members of the ␣-arrestin family (Ldb19/Art1, Rod1/Art4, and Rog3/ Art7) contribute to Ste2 desensitization and internalization, and they do so by discrete mechanisms. We provide genetic and biochemical evidence that Ldb19 and Rod1 recruit Rsp5 to Ste2 via PPXY motifs in their C-terminal regions; in contrast, the arrestin fold domain at the N terminus of Rog3 is sufficient to promote adaptation. Finally, we show that Rod1 function requires calcineurin-dependent dephosphorylation.

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CNP-1 (ARRD-17), a Novel Substrate of Calcineurin, Is Critical for Modulation of Egg-Laying and Locomotion in Response to Food and Lysine Sensation in Caenorhabditis elegans

Cited by 17 publications

References 45 publications

Mammalian Alpha Arrestins Link Activated Seven Transmembrane Receptors to Nedd4 Family E3 Ubiquitin Ligases and Interact with Beta Arrestins

Mammalian Alpha Arrestins Link Activated Seven Transmembrane Receptors to Nedd4 Family E3 Ubiquitin Ligases and Interact with Beta Arrestins

A Calcineurin-dependent Switch Controls the Trafficking Function of α-Arrestin Aly1/Art6

Specific α-Arrestins Negatively Regulate Saccharomyces cerevisiae Pheromone Response by Down-Modulating the G-Protein-Coupled Receptor Ste2

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