Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein.
CPEB-mediated translation is important in early development and neuronal synaptic plasticity. Here, we describe a new eukaryotic initiation factor 4E (eIF4E) binding protein, Neuroguidin (Ngd), and its interaction with CPEB. In the mammalian nervous system, Ngd is detected as puncta in axons and dendrites and in growth cones and filopodia. Ngd contains three motifs that resemble those present in eIF4G, 4EBP, Cup, and Maskin, all of which are eIF4E binding proteins. Ngd binds eIF4E directly, and all three motifs must be deleted to abrogate the interaction between these two proteins. In injected Xenopus oocytes, Ngd binds CPEB and, most importantly, represses translation in a cytoplasmic polyadenylation element (CPE)-dependent manner. In Xenopus embryos, Ngd is found in both neural tube and neural crest cells. The injection of morpholino-containing antisense oligonucleotides directed against ngd mRNA disrupts neural tube closure and neural crest migration; however, the wild-type phenotype is restored by the injection of a rescuing ngd mRNA. These data suggest that Ngd guides neural development by regulating the translation of CPE-containing mRNAs.
Jung
Mi-Young
MY
Program in Molecular Medicine, University of Massachusetts Medical School, Suite 204, 373 Plantation St., Worcester MA 01605, USA.
Lorenz
Lori
L
Richter
Joel D
JD
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000166:cytology; D009474:Neurons / Q000166:cytology; D011485:Protein Binding; D014176:Protein Biosynthesis; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014714:Vertebrates / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors
D039561:Eukaryotic Initiation Factor-4E; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C511175:neuroguidin protein, mouse; C490387:Cpeb1 protein, mouse; D039221:mRNA Cleavage and Polyadenylation Factors