Abstract
How compartment-specific local proteomes are generated and maintained is inadequately understood, particularly in neurons, which display extreme asymmetries. Here we show that local enrichment of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in axons of Drosophila mushroom body neurons is necessary for cellular plasticity and associative memory formation. Enrichment is achieved via enhanced axoplasmic translation of CaMKII mRNA, through a mechanism requiring the RNA-binding protein Mub and a 23-base Mub-recognition element in the CaMKII 3′ UTR. Perturbation of either dramatically reduces axonal, but not somatic, CaMKII protein without altering the distribution or amount of mRNA in vivo, and both are necessary and sufficient to enhance axonal translation of reporter mRNA. Together, these data identify elevated levels of translation of an evenly distributed mRNA as a novel strategy for generating subcellular biochemical asymmetries. They further demonstrate the importance of distributional asymmetry in the computational and biological functions of neurons.
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•Drosophila CaMKII becomes enriched in mushroom body axons via local synthesis•A 23 bp element in the CaMKII 3′ UTR is required for the synaptic enrichment of CaMKII•Mub, the Drosophila polyC-binding protein, is required for local CaMKII synthesis•Axonal enrichment of CaMKII is required for behavioral and cellular plasticity
Neurons have specialized structures for information transfer. Chen et al. show that CaMKII, a protein critical for learning, is concentrated at synapses of the Drosophila mushroom body by local synthesis. The synthesis signal resides in 23 bp of the mRNA 3′ UTR and is read out by Mub, the polyC-binding protein homolog of the fly.