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1、DiseasesAssociatedwithGprotein-CoupledReceptorsGivingBywangnishaXiexixiuZhangwenshanWangjingbriefintroductionThehumangenomemayencodeasmanyas2000differentGPCRs.Theirimportanceinhumanbiologyisreflectedbythefactthatmorethanone-quarterofallprescriptiondrugsactasligandsthatbindtothishu
2、gesuperfamilyofreceptors.AnumberofinheriteddisordershavebeentracedtodefectsinbothGPCRsandheterotrimericGprotein.SeveraldiseasesCongenitalnephrogenicdiabetesinsipidus(CNDI)Congenitalnephrogenicdiabetesinsipidus(CNDI)isarareinheriteddiseaseinwhichinfantssufferseriousdehydrationasthe
3、resultofaninabilityoftheirkidneystoproduceaconcentratedurine.Ifnotdiagnosedpromptly,thechronicdehydrationcanproducementalretardation,inadequategrowth,andevendeath.CNDI先天性腎源性尿崩癥疾病屬性：罕見的遺傳性疾病主要癥狀：由于腎臟集合管對(duì)抗利尿激素不起反應(yīng)而致尿濃縮障礙，出現(xiàn)多飲、多尿和尿比重降低?；疾〉膵雰旱哪I臟缺乏產(chǎn)生終尿的能力，他們會(huì)遭受到嚴(yán)重的脫水。如果沒有及時(shí)地診斷治療，這種慢性的的
4、脫水會(huì)引發(fā)智障礙、生長(zhǎng)遲緩、甚至是死亡.病理檢查：抗利尿激素受體發(fā)生錯(cuò)誤造成信號(hào)傳導(dǎo)問題，導(dǎo)致CNDI腎臟的細(xì)胞失去了對(duì)抗利尿激素的應(yīng)答能力.1Thecauseofthediseaseresultfrommutationsinaquaporins,Thewaterchannelsoftheplasmamembrane.Thecauseofthedisease圖示為腎臟的水通道蛋白(Aquaporin-2)，這是一個(gè)六次跨膜的蛋白質(zhì)，氮末端和碳末端都在膜內(nèi)，有三個(gè)細(xì)胞外環(huán)和兩個(gè)細(xì)胞內(nèi)環(huán)。圖上的黑點(diǎn)表示突變位點(diǎn)，這些突變位點(diǎn)的變化導(dǎo)致水通道蛋白的失活或通透性增
5、強(qiáng)，相應(yīng)表現(xiàn)為病人脫水或不排尿。相應(yīng)于CNDI的突變?yōu)镼57POtherreasonsInmostcase,however,thefaultliesinthevasopressin(后葉升壓素，即抗利尿素)receptor,whichistypicallyshortenedastheresultofamutationthatintroducesastopcodonintothemRNA,causingprematureterminationofpolypeptidesynthesis.Adifferenttypeofdebilitatingmutation
6、inthissameGPCRleadstoanaminoacidsubstitutionatthejunctionbetweenthethirdtransmembranesegmentandthesecondintracellularloop.Eventhoughthisreceptorcanstillbindvasopressinatitsexternalsurface,thereceptorcannotactivatetheGproteinandthuscannotpassthesignaldownstreamtotheeffector.12.3New
7、discoveryinkoreaHermotherandherfatherarenotsufferedfromthisdisease.Thegirl’sdiseasewasthoughttobeanautosomalrecessiveform.Ala(GCC)toAsp(GAC)inexon1inheritedformherfatherandArg(CGC)toHis(CAC)inexon3inheritedfromhermother.
