title: DSCR1 interacts with FMRP and is required for spine morphogenesis and local protein synthesis.
abstract: Most common genetic factors known to cause intellectual disability are Down syndrome and Fragile X syndrome. However, the underlying cellular and molecular mechanisms of intellectual disability remain unclear. Recently, dendritic spine dysmorphogenesis and impaired local protein synthesis are posited to contribute to the cellular mechanisms of intellectual disability. Here, we show that Down syndrome critical region1 (DSCR1) interacts with Fragile X mental retardation protein (FMRP) and regulates both dendritic spine morphogenesis and local protein synthesis. Interestingly, decreasing the level of FMRP restores the DSCR1-induced changes in dendritic spine morphology. Our results imply that DSCR1 is a novel regulator of FMRP and that Fragile X syndrome and Down syndrome may share disturbances in common pathways that regulate dendritic spine morphology and local protein synthesis.
authors.affiliation: Department of Biology, Indiana University, Bloomington, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: John Z
authors.initials: JZ
authors.lastname: Zhu
authors.forename: Karen T
authors.initials: KT
authors.lastname: Chang
authors.forename: Kyung-Tai
authors.initials: KT
authors.lastname: Min
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D049229:Dendritic Spines / Q000378:metabolism*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism / Q000502:physiology*; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis; D009124:Muscle Proteins / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; C511512:DSCR1 protein, mouse; C108612:RCAN1 protein, human