title: Expression of fragile X mental retardation-1 gene with nuclear export signal mutation changes the expression profiling of mouse cerebella immortal neuronal cell.
abstract: Fragile X syndrome (FXS) is the most frequent cause of inherited mental retardation and is largely caused by a loss of expression of fragile X mental retardation protein (FMRP), encoded by fragile X retardation gene-1 (Fmr1). FMRP is a multifunction protein, with intrinsic RNA-binding properties, which is a component of ribonucleoprotein complex associated with polyribosomes. The properties of FMRP indicate that it might participate in post-transcriptional processes in the regulation of some mRNA species, including localization, stability and translational control. However, the function of FMRP related to the pathologenesis in FXS is largely unknown. Many efforts were undertaken to identify the putative specific RNA targets as well as the FMRP-related proteins and to identify the effect of FMRP absence on the corresponding proteins. Here we present our efforts using proteomics approach to explore the differential expression profiling of mouse cerebella immortal cell, in which we changed the expression of FMRP by expressing Fmr1 gene with nuclear export signal (NES) mutation. This mutation makes FMRP unable to shuttle from nucleus to cytoplasm and leads to nuclear instead of cytoplasmic location as usual, which was hypothesized to affect the pathways of groups of RNAs or proteins related with FMRP. In present study, 56 proteins were found to be differentially expressed in transfected R2 neuronal cells, including 16 decreased expressions and 40 increased expressions. The differentially expressed proteins play roles in diverse physiological processes, such as neuronal plasticity, spermatogenesis and craniofacial and limb development etc. In addition, the expressions of three mRNA identified as FMRP targets in fragile X cell were tested in present model cells. All these results provide new insights to the role of FMRP in the disease.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P.R. China.
authors.forename: LiPing
authors.initials: L
authors.lastname: Hu
authors.forename: YuTing
authors.initials: Y
authors.lastname: Chen
authors.forename: Stefan
authors.initials: S
authors.lastname: Evers
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology; D015180:Electrophoresis, Gel, Two-Dimensional; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases; D009474:Neurons / Q000166:cytology; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D054778:NM23 Nucleoside Diphosphate Kinases; D009687:Nuclear Proteins; D009701:Nucleoside-Diphosphate Kinase; D011506:Proteins; D012333:RNA, Messenger; D044763:Ubiquitin-Conjugating Enzymes; C497684:Fmr1 protein, mouse