The adaptor function of Trs20 in mammalian TRAPPs explains Trs20-associated SEDT and Trsl20-associated congenital intellectual disability
作者单位：School of Biomedical Sciences and 2Epithelial Cell Biology Research CenterThe Chinese University of Hong KongShatinN.T.Hong Kong SARP.R.China
会议名称：《“细胞活动 生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会》
会议日期：2011年
学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
关 键 词：TRAPP SEDT Vesicle traffic
摘 要：The TRAPP(Transport protein particle) complex is a conserved protein complex functioning at various steps in vesicle *** yeast has three functionally and structurally distinct forms, TRAPPⅠ,ⅡandⅢ,emerging evidence suggests that mammalian TRAPP complex may be different. Mutations in the Trs20 subunit cause X-linked spondyloepiphyseal dysplasia tarda,while mutations in the Trs120 subunit cause postnatal mental retardation with *** structural interplay between these subunits found in mammalian equivalent of TRAPPⅠand those specific to TRAPPⅡand TRAPPⅢremains largely unknown and we undertook the present study to examine the interaction between these ***,we reveal that the mammalian equivalent of the TRAPPⅡcomplex is structurally distinct from the yeast counterpart thus leading to insight into mechanism of *** analyzed how TRAPPⅡ-or TRAPPⅢ- specific subunits interact with the six-subunit core complex of TRAPP by co-immunoprecipitation in mammalian ***20 binds to TRAPPⅡ-specific subunit Trsl20,which in turn binds to ***,Trs20 can also bind to the putative TRAPPⅢ-specific subunit,Trs85. Endogenous Trsl20-positive TRAPPⅡcomplex does not contain Trs85,suggesting that Trs20 binds to either Trs120 or Trs85 during the formation of the mammalian equivalents of TRAPPⅡor TRAPPⅢ, ***,Trs20 serves as an adaptor for the formation of these complexes.A disease-causing mutation of Trs20,D47Y,failed to interact with either Trs120 or Trs85,suggesting that aspartate 47 in Trs20 is at or near the site of interaction with Trs120 or Trs85,mediating the formation of TRAPPⅡand/or TRAPPⅢ.Furthermore,disease-causing deletional mutants of Trs120 all failed to interact with Trs20 and ***20 serves as an adaptor for the formation of TRAPPⅡor TRAPPⅢin mammalian *** mammalian equivalent of TRAPPⅡis likely different from the yeast TRAPPⅡstructurally.