BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development.
Local regulation of mRNA translation plays an important role in axon guidance, synaptic development, and neuronal plasticity. Little is known, however, regarding the mechanisms that control translation in neurons, and only a few mRNAs have been identified that are locally translated within axon and dendrites. Using Affymetrix gene arrays to identify mRNAs that are newly associated with polysomes after exposure to BDNF, we identified subsets of mRNAs for which translation is enhanced in neurons at different developmental stages. In mature neurons, many of these mRNAs encode proteins that are known to function at synapses, including CamKIIalpha, NMDA receptor subunits, and the postsynaptic density (PSD) scaffolding protein Homer2. BDNF regulates the translation of Homer2 locally in the synaptodendritic compartment by activating translational initiation via a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway. These findings suggest that BDNF likely regulates synaptic function by inducing the local synthesis of numerous synaptic proteins. The local translation of the cytoskeleton-associated protein Homer2 in particular might have important implications for growth cone dynamics and dendritic spine development.
Schratt
Gerhard M
GM
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115, USA.
Nigh
Elizabeth A
EA
Chen
Wen G
WG
Hu
Linda
L
Greenberg
Michael E
ME
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D003712:Dendrites / Q000737:chemistry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D000072233:Homer Scaffolding Proteins; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011132:Polyribosomes / Q000187:drug effects / Q000235:genetics; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000145:classification; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction; D013569:Synapses / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D058570:TOR Serine-Threonine Kinases
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; C000606626:Homer2 protein, rat