Tubby is required for trafficking g protein-coupled receptors to neuronal cilia 英文参考文献.docVIP

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Tubby is required for trafficking g protein-coupled receptors to neuronal cilia 英文参考文献.doc

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Tubby is required for trafficking g protein-coupled receptors to neuronal cilia 英文参考文献

Sunetal.Cilia2012,1:21 /content/1/1/21 RESEARCH OpenAccess TubbyisrequiredfortraffickingGprotein-coupled receptorstoneuronalcilia XunSun1,JamesHaley1,OlegVBulgakov1,XueCai2,JamesMcGinnis2andTiansenLi1* PleaseseerelatedCommentaryarticlebyMukhopadhyayandJackson/content/2/1/1 Background The tubby-like proteins are defined by a highly con- Abstract served carboxyl terminal half of their primary sequence known as the tubby signature domain [1,2]. This family of proteins includes the prototype tubby, and TULP1, 2 and 3, for tubby-like proteins 1, 2 and 3 [3-5]. Other than members of the tubby family, search of sequence databases reveals no significant homology with known Background:Tubbyisthefoundingmemberofthe tubby-likefamilyofproteins.Thenaturallyoccurring tubbymutationinmicecausesretinitispigmentosa, hearinglossandobesity.Tubbyhasbeenproposedto functionasanaccessoryfactorinciliarytrafficking.We directlyexaminedarolefortubbyinciliarytrafficking proteinsorfunctionalmotifs.Thetubbygene(Tub )was invivo. originally discovered by way of a spontaneously arisen Methods:Weusedimmunofluoresencelabelingto obesitymodelinmice,andothermembersofthefamily examinethesubcellularlocalizationofrhodopsin, were subsequently identified by homology cloning [3]. somatostatinreceptor3(SSTR3)andmelanin Mutationsinhuman TULP1areacauseofretinitis pig- concentratinghormonereceptor1(MCHR1),allof mentosa [6]. Loss of TULP1 function in mice replicates whichareGprotein-coupledreceptors(GPCR),inthe this rapid photoreceptor degeneration phenotype [7,8]. retinaandbrainofwildtype(WT)andtubbymutant Prior to photoreceptor degeneration in the mouse retina, mice. pronounced ectopic distribution of rhodopsin is apparent Results:Intubbymouseretina,rhodopsinisnotfully transportedacrosstheconnectingciliatotheouter segmentswithensuingphotoreceptordegeneration.In thetubbymousebrain,SSTR3andMCHR1failto localizeattheneuronalprimaryciliainregionswhere thesereceptorsplaycriticalrolesinneuralsignaling.The tubbymuta