Fragile X mental retardation protein interacts with the RNA-binding protein Caprin1 in neuronal RiboNucleoProtein complexes [corrected].
Fragile X syndrome is caused by the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein. FMRP is associated with messenger RiboNucleoParticles (mRNPs) present in polyribosomes and its absence in neurons leads to alteration in synaptic plasticity as a result of translation regulation defects. The molecular mechanisms by which FMRP plays a role in translation regulation remain elusive. Using immunoprecipitation approaches with monoclonal Ab7G1-1 and a new generation of chicken antibodies, we identified Caprin1 as a novel FMRP-cellular partner. In vivo and in vitro evidence show that Caprin1 interacts with FMRP at the level of the translation machinery as well as in trafficking neuronal granules. As an RNA-binding protein, Caprin1 has in common with FMRP at least two RNA targets that have been identified as CaMKIIα and Map1b mRNAs. In view of the new concept that FMRP species bind to RNA regardless of known structural motifs, we propose that protein interactors might modulate FMRP functions.
Centre de Recherche, Institut Universitaire en Santé Mentale, Québec, PQ, Canada.
Rachid
R
El Fatimy
Sandra
S
Tremblay
Alain Y
AY
Dury
Samuel
S
Solomon
Paul
P
De Koninck
John W
JW
Schrader
Edouard W
EW
Khandjian
D020816:Amino Acid Motifs; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009474:Neurons / Q000378:metabolism*; D011132:Polyribosomes / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D018797:Cell Cycle Proteins; D017931:DNA Primers; D051860:Fragile X Messenger Ribonucleoprotein 1; D008869:Microtubule-Associated Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C486562:CAPRIN1 protein, human; C486565:Caprin1 protein, mouse; C497683:FMR1 protein, human; C475491:MAP1B protein, human