A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P

被引:283
作者
Schenck, A
Bardoni, B
Moro, A
Bagni, C
Mandel, JL
机构
[1] Univ Louis Pasteur Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch, Strasbourg, France
[2] Univ Roma Tor Vergata, Dipartimento Biol, I-00133 Rome, Italy
[3] Univ Pavia, Dipartimento Patol Umana, I-27100 Pavia, Italy
[4] Univ Pavia, Dipartimento Patol Umana & Ereditaria, Sez Biol Gen & Genet Med, I-27100 Pavia, Italy
关键词
D O I
10.1073/pnas.151231598
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex. Although its function is poorly understood, various observations suggest a role in local protein translation at neuronal dendrites and in dendritic spine maturation. We present here the identification of CYFIP1/2 (Cytoplasmic FMRP Interacting Proteins) as FMRP interactors. CYFIP1/2 share 88% amino acid sequence identity and represent the two members in humans of a highly conserved protein family. Remarkably, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P/2P, CYFIP1 interacts exclusively with FMRP, FMRP-CYFIP interaction involves the domain of FMRP also mediating homo- and heteromerization, thus suggesting a competition between interaction among the FXR proteins and interaction with CYFIP, CYFIP1/2 are proteins of unknown function, but CYFIP1 has recently been shown to interact with the small GTPase Rad, which is implicated in development and maintenance of neuronal structures. Consistent with FMRP and Rad localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts.
引用
收藏
页码:8844 / 8849
页数:6
相关论文
共 36 条
  • [1] Dissecting FMR1, the protein responsible for fragile X syndrome, in its structural and functional domains
    Adinolfi, S
    Bagni, C
    Musco, G
    Gibson, T
    Mazzarella, L
    Pastore, A
    [J]. RNA, 1999, 5 (09) : 1248 - 1258
  • [2] FMR1 PROTEIN - CONSERVED RNP FAMILY DOMAINS AND SELECTIVE RNA-BINDING
    ASHLEY, CT
    WILKINSON, KD
    REINES, D
    WARREN, ST
    [J]. SCIENCE, 1993, 262 (5133) : 563 - 566
  • [3] Chemical stimulation of synaptosomes modulates α-Ca2+/calmodulin-dependent protein kinase II mRNA association to polysomes
    Bagni, C
    Mannucci, L
    Dotti, CG
    Amaldi, F
    [J]. JOURNAL OF NEUROSCIENCE, 2000, 20 (10) : art. no. - RC76
  • [4] Immunocytochemical and biochemical characterization of FMRP, FXR1P, and FXR2P in the mouse
    Bakker, CE
    Otero, YD
    Bontekoe, C
    Raghoe, P
    Luteijn, T
    Hoogeveen, AT
    Oostra, BA
    Willemsen, R
    [J]. EXPERIMENTAL CELL RESEARCH, 2000, 258 (01) : 162 - 170
  • [5] A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein
    Bardoni, B
    Schenck, A
    Mandel, JL
    [J]. HUMAN MOLECULAR GENETICS, 1999, 8 (13) : 2557 - 2566
  • [6] Nucleolin interacts with several ribosomal proteins through its RGG domain
    Bouvet, P
    Diaz, JJ
    Kindbeiter, K
    Madjar, JJ
    Amalric, F
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (30) : 19025 - 19029
  • [7] Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein
    Brown, V
    Small, K
    Lakkis, L
    Feng, Y
    Gunter, C
    Wilkinson, KD
    Warren, ST
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (25) : 15521 - 15527
  • [8] Ceman S, 1999, MOL CELL BIOL, V19, P7925
  • [9] Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits
    Comery, TA
    Harris, JB
    Willems, PJ
    Oostra, BA
    Irwin, SA
    Weiler, IJ
    Greenough, WT
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) : 5401 - 5404
  • [10] The fragile X mental retardation protein is associated with poly(A)(+) mRNA in actively translating polyribosomes
    Corbin, F
    Bouillon, M
    Fortin, A
    Morin, S
    Rousseau, F
    Khandjian, EW
    [J]. HUMAN MOLECULAR GENETICS, 1997, 6 (09) : 1465 - 1472