Facilitation of dendritic mRNA transport by CPEB
Program in Molecular Medicine
Animals; Cell Line; Dendrites; Green Fluorescent Proteins; Hippocampus; Luminescent Proteins; Microtubules; Molecular Motor Proteins; RNA, Messenger; Rats; Recombinant Fusion Proteins; Transcription Factors; mRNA Cleavage and Polyadenylation Factors
Life Sciences | Medicine and Health Sciences
In neurons, the proteins derived from mRNAs localized in dendrites have been implicated in synaptic plasticity. The cytoplasmic polyadenylation element (CPE), a cis element in the 3'-UTRs of specific dendritic mRNAs, promotes cytoplasmic polyadenylation-induced translation in response to synaptic stimulation. Here, we demonstrate that the CPE and its binding protein CPEB facilitate mRNA transport to dendrites. In rat hippocampal neurons infected with recombinant viruses, the CPE is sufficient to direct a reporter RNA into dendrites. CPEB-GFP protein forms RNA-containing particles that are transported into dendrites in a microtubule-dependent fashion at an average velocity of 4-8 microm/min. Such particles also contain maskin, a CPEB-associated factor that mediates cap-dependent translational repression of CPE-containing mRNA, and the molecular motors dynein and kinesin. Overexpression of CPEB in neurons promotes the transport of CPE-containing endogenous MAP2 mRNA to dendrites, whereas overexpression of a mutant CPEB that is defective for interaction with molecular motors inhibits this transport. In neurons derived from CPEB knockout mice, the dendritic transport of a CPE-containing reporter RNA is reduced. These results suggest a mechanism whereby CPE-containing mRNAs can be transported to dendrites in a translationally dormant form, but activated at synapses in response to NMDA receptor stimulation.
DOI of Published Version
Genes Dev. 2003 Mar 1;17(5):638-53. Link to article on publisher's site
Genes and development
Huang, Yi-Shuian; Carson, John H.; Barbarese, Elisa; and Richter, Joel D., "Facilitation of dendritic mRNA transport by CPEB" (2003). Open Access Articles. 582.