title: HuD interacts with Bdnf mRNA and is essential for activity-induced BDNF synthesis in dendrites.
abstract: Highly specific activity-dependent neuronal responses are necessary for modulating synapses to facilitate learning and memory. We present evidence linking a number of important processes involved in regulating synaptic plasticity, suggesting a mechanistic pathway whereby activity-dependent signaling, likely through protein kinase C (PKC)-mediated phosphorylation of HuD, can relieve basal repression of Bdnf mRNA translation in dendrites, allowing for increased TrkB signaling and synaptic remodeling. We demonstrate that the neuronal ELAV family of RNA binding proteins associates in vivo with several Bdnf mRNA isoforms present in the adult brain in an activity-dependent manner, and that one member, HuD, interacts directly with sequences in the long Bdnf 3' untranslated region (3'UTR) and co-localizes with Bdnf mRNA in dendrites of hippocampal neurons. Activation of PKC leads to increased dendritic translation of mRNAs containing the long Bdnf 3'UTR, a process that is dependent on the presence of HuD and its phosphorylation at threonine residues 149 and/or 165. Thus, we found a direct effect of HuD on regulating translation of dendritic Bdnf mRNAs to mediate local and activity-dependent increases in dendritic BDNF synthesis.
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, D.C., United States of America.
authors.forename: Filip
authors.initials: F
authors.lastname: Vanevski
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, D.C., United States of America.
authors.forename: Baoji
authors.initials: B
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics*; D003712:Dendrites / Q000378:metabolism*; D051959:ELAV Proteins / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D013912:Threonine / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D019208:Brain-Derived Neurotrophic Factor; D051959:ELAV Proteins; D013912:Threonine; D011493:Protein Kinase C