Program in Molecular Medicine
Animals; Axons; Base Sequence; Cytoplasm; Fluorescent Antibody Technique; Gene Expression Regulation; In Situ Hybridization; Molecular Sequence Data; Plasmids; Polyadenylation; Protein Biosynthesis; RNA, Messenger; Retinal Ganglion Cells; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors; Xenopus; Xenopus Proteins; mRNA Cleavage and Polyadenylation Factors
Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology
BACKGROUND: Translation in axons is required for growth cone chemotropic responses to many guidance cues. Although locally synthesized proteins are beginning to be identified, how specific mRNAs are selected for translation remains unclear. Control of poly(A) tail length by cytoplasmic polyadenylation element (CPE) binding protein 1 (CPEB1) is a conserved mechanism for mRNA-specific translational regulation that could be involved in regulating translation in axons.
RESULTS: We show that cytoplasmic polyadenylation is required in Xenopus retinal ganglion cell (RGC) growth cones for translation-dependent, but not translation-independent, chemotropic responses in vitro, and that inhibition of CPE binding through dominant-negative interference severely reduces axon outgrowth in vivo. CPEB1 mRNA transcripts are present at low levels in RGCs but, surprisingly, CPEB1 protein was not detected in eye or brain tissue, and CPEB1 loss-of-function does not affect chemotropic responses or pathfinding in vivo. UV cross-linking experiments suggest that CPE-binding proteins other than CPEB1 in the retina regulate retinal axon development.
CONCLUSION: These results indicate that cytoplasmic polyadenylation and CPE-mediated translational regulation are involved in retinal axon development, but that CPEB1 may not be the key regulator of polyadenylation in the developing retina.
Lin, Andrew C.; Tan, Chin Lik; Lin, Chien-Ling; Strochlic, Laure; Huang, Yi-Shuian; Richter, Joel D.; and Holt, Christine E., "Cytoplasmic polyadenylation and cytoplasmic polyadenylation element-dependent mRNA regulation are involved in Xenopus retinal axon development" (2009). Open Access Articles. 2274.