Regulation of Protein Translation in Neurons
During nervous system development, the processes of axon guidance and
synapse formation are dependent on new protein synthesis. Moreover, higher brain functions that are related to synaptic plasticity,
such as learning and memory, are also disrupted by inhibitors of protein translation. Although the bulk of mRNAs are translated in
the neuronal cell body, local translation of specific mRNAs has been shown to be of particular importance for the regulation of
protein expression within axons and dendrites. Several mRNAs, as well as components of the translational machinery, have been detected
in dendrites and axon growth cones, and extracellular stimulation regulates the translation of these mRNAs. 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 axons and dendrites.
Using Affymetrix gene arrays to identify mRNAs that are newly associated with polysomes after exposure to brain-derived neurotrophic factor (BDNF), we have 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 CamKIIa, 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, and the further characterization of these BDNF-regulated mRNAs should enhance our understanding of how BDNF regulates axonal and dendritic function.
Schratt GM, Nigh EA, Chen WG, Hu L, Greenberg ME. BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development. Neurosci. 2004; 24(33):7366-7377.
Other research areas:
Activity-Dependent Gene Transcription
Neuronal Cell Fate Determination
Neuronal Survival and Apoptosis
Synapse Formation and Maintenance
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