{"doi":"10.1111/jnc.13366","title":"The effect of phosphorylation on arrestin–rhodopsin interaction in the squid visual system","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:label/><jats:p>Invertebrate visual opsins are G protein‐coupled receptors coupled to retinoid chromophores that isomerize reversibly between inactive rhodopsin and active metarhodopsin upon absorption of photons of light. The squid visual system has an arrestin protein that binds to metarhodopsin to block signaling to G<jats:sub>q</jats:sub> and activation of phospholipase C. Squid rhodopsin kinase (<jats:styled-content style=\"fixed-case\">SQRK</jats:styled-content>) can phosphorylate both metarhodopsin and arrestin, a dual role that is unique among the G protein‐coupled receptor kinases. The sites and role of arrestin phosphorylation by <jats:styled-content style=\"fixed-case\">SQRK</jats:styled-content> were investigated here using recombinant proteins. Arrestin was phosphorylated on serine 392 and serine 397 in the C‐terminus. Unphosphorylated arrestin bound to metarhodopsin and phosphorylated metarhodopsin with similar high affinities (<jats:italic>K</jats:italic><jats:sub>d</jats:sub> 33 and 21 nM respectively), while phosphorylation of arrestin reduced the affinity 3‐ to 5‐fold (<jats:italic>K</jats:italic><jats:sub>d</jats:sub> 104 nM). Phosphorylation of metarhodopsin slightly increased the dissociation of arrestin observed during a 1 hour incubation. Together these studies suggest a unique role for <jats:styled-content style=\"fixed-case\">SQRK</jats:styled-content> in phosphorylating both receptor and arrestin and inhibiting the binding of these two proteins in the squid visual system.</jats:p></jats:sec><jats:sec><jats:label/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/jnc13366-fig-0010-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>\nInvertebrate visual systems are inactivated by arrestin binding to metarhodopsin that does not require receptor phosphorylation. Here we show that squid rhodopsin kinase phosphorylates arrestin on two serines (S392,S397) in the C‐terminus and phosphorylation decreases the affinity of arrestin for squid metarhodopsin. Metarhodopsin phosphorylation has very little effect on arrestin binding but does increase arrestin dissociation.</jats:p></jats:sec>","journal":"Journal of Neurochemistry","year":2015,"id":679380,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353312,"name":"Wei‐Lin Ou","orcid":"0000-0002-8069-5927","position":1,"is_corresponding":false},{"id":828398,"name":"Xinyu Guan","orcid":"0000-0003-2366-9375","position":2,"is_corresponding":false},{"id":1752913,"name":"Kim S. Sugamori","orcid":null,"position":3,"is_corresponding":false},{"id":1132763,"name":"Abhishek Bandyopadhyay","orcid":"0000-0001-7062-4343","position":4,"is_corresponding":false},{"id":292043,"name":"Oliver P. Ernst","orcid":"0000-0002-8863-9444","position":5,"is_corresponding":false},{"id":1775030,"name":"Jane Mitchell","orcid":null,"position":6,"is_corresponding":false},{"id":1775029,"name":"Kelly A. Robinson","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The effect of phosphorylation on arrestin–rhodopsin interaction in the squid visual system","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:label/><jats:p>Invertebrate visual opsins are G protein‐coupled receptors coupled to retinoid chromophores that isomerize reversibly between inactive rhodopsin and active metarhodopsin upon absorption of photons of light. The squid visual system has an arrestin protein that binds to metarhodopsin to block signaling to G<jats:sub>q</jats:sub> and activation of phospholipase C. Squid rhodopsin kinase (<jats:styled-content style=\"fixed-case\">SQRK</jats:styled-content>) can phosphorylate both metarhodopsin and arrestin, a dual role that is unique among the G protein‐coupled receptor kinases. The sites and role of arrestin phosphorylation by <jats:styled-content style=\"fixed-case\">SQRK</jats:styled-content> were investigated here using recombinant proteins. Arrestin was phosphorylated on serine 392 and serine 397 in the C‐terminus. Unphosphorylated arrestin bound to metarhodopsin and phosphorylated metarhodopsin with similar high affinities (<jats:italic>K</jats:italic><jats:sub>d</jats:sub> 33 and 21 nM respectively), while phosphorylation of arrestin reduced the affinity 3‐ to 5‐fold (<jats:italic>K</jats:italic><jats:sub>d</jats:sub> 104 nM). Phosphorylation of metarhodopsin slightly increased the dissociation of arrestin observed during a 1 hour incubation. Together these studies suggest a unique role for <jats:styled-content style=\"fixed-case\">SQRK</jats:styled-content> in phosphorylating both receptor and arrestin and inhibiting the binding of these two proteins in the squid visual system.</jats:p></jats:sec><jats:sec><jats:label/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/jnc13366-fig-0010-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>\nInvertebrate visual systems are inactivated by arrestin binding to metarhodopsin that does not require receptor phosphorylation. Here we show that squid rhodopsin kinase phosphorylates arrestin on two serines (S392,S397) in the C‐terminus and phosphorylation decreases the affinity of arrestin for squid metarhodopsin. Metarhodopsin phosphorylation has very little effect on arrestin binding but does increase arrestin dissociation.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26375013","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"RGPIN 171213‐09","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"Wiley Online Library User Agreement","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fjnc.13366","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jnc.13366","host_type":"publisher"},{"url":"https://doi.org/10.1111/jnc.13366","host_type":""},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jnc.13366","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/26375013","host_type":""},{"url":"https://dx.doi.org/10.1111/jnc.13366","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Animals","Rhodopsin","Serine","Eye Proteins","Arrestin","Signal Transduction","Phosphorylation","Light","Molecular Sequence Data","Decapodiformes","Vision, Ocular","Photoreceptor Cells, Invertebrate"],"keywords":["Rhodopsin","Visual system","Invertebrate","Arrestin","Squid","Rhodopsin Kinase","Light","Molecular Sequence Data","Decapodiformes","Serine","Animals","Photoreceptor Cells, Invertebrate","Phosphorylation","Eye Proteins","Vision, Ocular","Signal Transduction"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T13:03:18.832750Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}