{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:23:24Z","timestamp":1785435804437,"version":"3.56.0"},"posted":{"date-parts":[[2025,9,15]]},"group-title":"Neuroscience","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R21AA030319"],"award-info":[{"award-number":["R21AA030319"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R33DA041876"],"award-info":[{"award-number":["R33DA041876"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UL1TR002529"],"award-info":[{"award-number":["UL1TR002529"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30CA082709"],"award-info":[{"award-number":["P30CA082709"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>Loss of dopamine neurons in Parkinson disease (PD) leads to motor deficits. Dopamine D2 receptor (D2R) agonists treat PD-associated motor deficits by acting on postsynaptic receptors located within the striatum that have been upregulated due dopamine loss. However, mechanisms that contribute to increased D2R activity in PD to enhance D2R function are poorly described. Spinophilin is a protein phosphatase 1 targeting protein that is expressed in postsynaptic dendritic spines and interacts with postsynaptic D2Rs. However, how spinophilin regulates D2R function is unknown. In the current study, we found that genetic knockout of spinophilin limited the suppression of locomotion caused by the D2R agonist, quinpirole. Mechanistically, we found that spinophilin is required for quinpirole-induced increases in the interaction of the D2R with intracellular proteins, suggesting spinophilin mediates agonist-induced D2R internalization. Therefore, our data support future studies targeting the spinophilin\/D2R interaction to enhance the efficacy of current PD therapeutics.<\/jats:p>","DOI":"10.1101\/2025.09.09.675136","type":"posted-content","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:15:11Z","timestamp":1757956511000},"source":"Crossref","is-referenced-by-count":0,"title":["Striatal spinophilin enhances D2R interaction with cytosolic proteins to mediate persistent D2R agonist-induced locomotor suppression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-8312","authenticated-orcid":false,"given":"Basant","family":"Hens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1174-0920","authenticated-orcid":false,"given":"Whitney R.","family":"Smith-Kinneman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0049-0073","authenticated-orcid":false,"given":"Emma H.","family":"Doud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4756-9865","authenticated-orcid":false,"suffix":"II","given":"Anthony J.","family":"Baucum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025091801401224000_2025.09.09.675136v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(73)90175-5"},{"key":"2025091801401224000_2025.09.09.675136v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a070990"},{"key":"2025091801401224000_2025.09.09.675136v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15030770"},{"key":"2025091801401224000_2025.09.09.675136v1.4","doi-asserted-by":"publisher","DOI":"10.1177\/1756286419838096"},{"key":"2025091801401224000_2025.09.09.675136v1.5","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.3474"},{"key":"2025091801401224000_2025.09.09.675136v1.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009874107"},{"key":"2025091801401224000_2025.09.09.675136v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00025"},{"key":"2025091801401224000_2025.09.09.675136v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011038"},{"key":"2025091801401224000_2025.09.09.675136v1.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7731"},{"key":"2025091801401224000_2025.09.09.675136v1.10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.50.29819"},{"key":"2025091801401224000_2025.09.09.675136v1.11","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.09358"},{"key":"2025091801401224000_2025.09.09.675136v1.12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.28.19894"},{"key":"2025091801401224000_2025.09.09.675136v1.13","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12840"},{"key":"2025091801401224000_2025.09.09.675136v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.02.067"},{"key":"2025091801401224000_2025.09.09.675136v1.15","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-019-0434-7"},{"key":"2025091801401224000_2025.09.09.675136v1.16","doi-asserted-by":"publisher","DOI":"10.1101\/2022.05.24.493240"},{"key":"2025091801401224000_2025.09.09.675136v1.17","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4153076"},{"key":"2025091801401224000_2025.09.09.675136v1.18","doi-asserted-by":"publisher","DOI":"10.3390\/proteomes6040053"},{"key":"2025091801401224000_2025.09.09.675136v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.02.006"},{"key":"2025091801401224000_2025.09.09.675136v1.20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.722355"},{"key":"2025091801401224000_2025.09.09.675136v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.08.002"},{"key":"2025091801401224000_2025.09.09.675136v1.22","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1126\/science.1098274","article-title":"Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors. Science (New York","volume":"304","year":"2004","journal-title":"N.Y"},{"key":"2025091801401224000_2025.09.09.675136v1.23","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.23.634546"},{"key":"2025091801401224000_2025.09.09.675136v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03604-5"},{"key":"2025091801401224000_2025.09.09.675136v1.25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq973"},{"key":"2025091801401224000_2025.09.09.675136v1.26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"},{"key":"2025091801401224000_2025.09.09.675136v1.27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"2025091801401224000_2025.09.09.675136v1.28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw937"},{"key":"2025091801401224000_2025.09.09.675136v1.29","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890200304"},{"key":"2025091801401224000_2025.09.09.675136v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2022.12.008"},{"key":"2025091801401224000_2025.09.09.675136v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2018.06.001"},{"key":"2025091801401224000_2025.09.09.675136v1.32","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2553-4"},{"key":"2025091801401224000_2025.09.09.675136v1.33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900388200"},{"key":"2025091801401224000_2025.09.09.675136v1.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502418102"},{"key":"2025091801401224000_2025.09.09.675136v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.189"},{"key":"2025091801401224000_2025.09.09.675136v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(90)90186-4"},{"key":"2025091801401224000_2025.09.09.675136v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.06.014"},{"key":"2025091801401224000_2025.09.09.675136v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01608-1"},{"key":"2025091801401224000_2025.09.09.675136v1.39","doi-asserted-by":"publisher","DOI":"10.1101\/2023.08.28.554807"},{"key":"2025091801401224000_2025.09.09.675136v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.01.010"},{"key":"2025091801401224000_2025.09.09.675136v1.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1406459111"},{"key":"2025091801401224000_2025.09.09.675136v1.42","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-204644"},{"key":"2025091801401224000_2025.09.09.675136v1.43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208503200"},{"key":"2025091801401224000_2025.09.09.675136v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.12.024"},{"key":"2025091801401224000_2025.09.09.675136v1.45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304195200"},{"key":"2025091801401224000_2025.09.09.675136v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2004.11.016"},{"key":"2025091801401224000_2025.09.09.675136v1.47","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e32833a5c68"},{"key":"2025091801401224000_2025.09.09.675136v1.48","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.22.1016"},{"key":"2025091801401224000_2025.09.09.675136v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/35041572"},{"key":"2025091801401224000_2025.09.09.675136v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.12.002"},{"key":"2025091801401224000_2025.09.09.675136v1.51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1717194115"},{"key":"2025091801401224000_2025.09.09.675136v1.52","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-22-08305.2000"},{"key":"2025091801401224000_2025.09.09.675136v1.53","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhh101"},{"key":"2025091801401224000_2025.09.09.675136v1.54","doi-asserted-by":"publisher","DOI":"10.1002\/cne.11001"},{"key":"2025091801401224000_2025.09.09.675136v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9362"},{"key":"2025091801401224000_2025.09.09.675136v1.56","unstructured":"Who has parkinson\u2019s. https:\/\/www.parkinson.org\/understanding-parkinsons\/statistics#:~:text=The%20combined%20direct%20and%20indirect,up%20to%20%24100%2C000%20per%20person."},{"key":"2025091801401224000_2025.09.09.675136v1.57","unstructured":"Parkinson\u2019s Disease. https:\/\/www.ninds.nih.gov\/health-information\/disorders\/parkinsons-disease."},{"key":"2025091801401224000_2025.09.09.675136v1.58","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28632"},{"key":"2025091801401224000_2025.09.09.675136v1.59","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00676-7"},{"key":"2025091801401224000_2025.09.09.675136v1.60","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm159"},{"key":"2025091801401224000_2025.09.09.675136v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0221-2"},{"key":"2025091801401224000_2025.09.09.675136v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-023-01063-0"},{"key":"2025091801401224000_2025.09.09.675136v1.63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002804"},{"key":"2025091801401224000_2025.09.09.675136v1.64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610790104"},{"key":"2025091801401224000_2025.09.09.675136v1.65","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0066"},{"key":"2025091801401224000_2025.09.09.675136v1.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100994"},{"key":"2025091801401224000_2025.09.09.675136v1.67","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00144"},{"key":"2025091801401224000_2025.09.09.675136v1.68","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3014"},{"key":"2025091801401224000_2025.09.09.675136v1.69","doi-asserted-by":"publisher","DOI":"10.3390\/proteomes9010015"},{"key":"2025091801401224000_2025.09.09.675136v1.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.01.010"},{"key":"2025091801401224000_2025.09.09.675136v1.71","first-page":"441","article-title":"Targeted insertion of exogenous DNA into the eukaryotic genome by the Cre recombinase","volume":"2","year":"1990","journal-title":"New Biol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.09.675136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:01:35Z","timestamp":1782277295000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.09.09.675136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":71,"URL":"https:\/\/doi.org\/10.1101\/2025.09.09.675136","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.jpet.2025.103788","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,9,15]]},"subtype":"preprint"}}