ArrestinproteinsareafamilyofcellsignalingregulatorsofGprotein-coupledreceptors.Inmammalstherearefourarrestinisoforms;visualarrestin(s-antigenandarrestin-1)andconearrestin(arrestin-4)whicharelargelyconfinedtophotoreceptors.β-arrestin1(arrestin2)andβ-arrestin-2(arrestin-3)areubiquitousandregulatenon-visualGPCRs.
Image:ConfocalimageofapigretinawithArrestin-1(MO22141)ingreen.Visualarrestinismostabundantintheothersegments(OS)andinnersurfaceoftheouternuclearlayer(ONL).Itcanbeusedtoidenfifycomponentsofrodphotoreceptorscells.RedstainingisFox2,anRNAbindingnuclearprotein.NuclearDNAwasrevealedwithDAPIinblue
Visualarrestinwasfirstdiscoveredasaresultoftheexperimentalmodelofhumanuveitis,anautoimmunediseaseoftheeye.Inthismodel,calledexperimentalallergicuveitis,animalswereinjectedwithextractsmadefromtheretinaofthesamespeciesmixedwithFreund’scompleteadjuvant.Theanimalsmountedastrongimmuneresponsetotheextract,andtheantibodyresponsewasusedtoidentifyseveralimmunogenicretinalproteins.OneofthesewascalledS-antigen,forsolubleantigen.Theproteinwasfoundtobeabundantinretina,about48kDainmolecularweight,andlocalizedintheoutersegmentsofthephotoreceptors.
Severalyearslater,HermannKühnandcolleaguesdiscoveredthatthisproteinbindstophosphorylatedrhodopsinandpreventsthisproteinfromactivatingtransducin.TransducinisatypicalheterotrimericGprotein,composedofαandβγsubunits.RhodopsinphosphorylationismediatedbyRhodopsinkinase(a.k.a.GRK1),theprototypicmemberofafamilyofGPCRkinases.SincetheS-antigenproteinarrestedtheactivityofrhodopsinitwasrenamedarrestin,andbecametheprototypicmemberofthearrestinproteinfamily.
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