
@article {110624,
	title = {Local translation provides the asymmetric distribution of CaMKII required for associative memory formation.},
	journal = {Curr Biol},
	year = {2022},
	month = {2022 May 04},
	abstract = {<p>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 Ca/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{\textquoteright} UTR. Perturbation of either dramatically reduces axonal, but not somatic, CaMKII protein without altering the distribution or amount of mRNA in\&nbsp;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.</p>
},
	issn = {1879-0445},
	doi = {10.1016/j.cub.2022.04.047},
	author = {Chen, Nannan and Zhang, Yunpeng and Adel, Mohamed and Kuklin, Elena A and Reed, Martha L and Mardovin, Jacob D and Bakthavachalu, Baskar and VijayRaghavan, K and Ramaswami, Mani and Griffith, Leslie C}
}
@article {24296,
	title = {The long 3{\textquoteright}UTR mRNA of CaMKII is essential for translation-dependent plasticity of spontaneous release in Drosophila melanogaster.},
	journal = {J Neurosci},
	year = {2017},
	month = {2017 Sep 27},
	abstract = {<p>A null mutation of the Drosophila calcium/calmodulin-dependent protein kinase II gene (CaMKII) was generated using homologous recombination. Null animals survive to larval and pupal stages due to a large maternal contribution of CaMKII mRNA, which consists of a short 3{\textquoteright}- u n t ranslated r egion (UTR) form lacking regulatory elements that guide local translation. The selective loss of the long 3{\textquoteright}UTR mRNA in CaMKII null larvae allows us to test its role in plasticity. Development and evoked function of the larval neuromuscular junction are surprisingly normal, but the resting rate of miniature excitatory junctional potentials (mEJPs) is significantly lower in CaMKII mutants. Mutants also lack the ability to increase mEJP rate in response to spaced depolarization, a type of activity-dependent plasticity shown to require both transcription and translation. Consistent with this, overexpression of miR-289 in wild-type animals blocks plasticity of spontaneous release. In addition to the defects in regulation of mEJP rate, CaMKII protein is largely lost from synapses in the mutant. All phenotypes are non-sex-specific and rescued by a fosmid containing the entire wild-type CaMKII locus, but only viability and CaMKII localization are rescued by genomic fosmids lacking the long 3{\textquoteright}UTR. This suggests that synaptic CaMKII accumulates by two distinct mechanisms: local synthesis requiring the long 3{\textquoteright}UTR form of CaMKII mRNA and a process which requires zygotic transcription of CaMKII mRNA. The origin of synaptic CaMKII also dictates its functionality. Locally translated CaMKII has a privileged role in regulation of spontaneous release which cannot be fulfilled by synaptic CaMKII from the other pool.SIGNIFICANCE STATEMENTAs a regulator of synaptic development and plasticity, CaMKII has important roles in both normal and pathological function of the nervous system. CaMKII shows high conservation between Drosophila and humans, underscoring the usefulness of Drosophila in modeling its function. Drosophila CaMKII null mutants remain viable throughout development, enabling morphological and electrophysiological characterization. While the structure of the synapse is normal, maternally contributed CaMKII does not localize to synapses. Zygotic production of CaMKII mRNA with a long 3{\textquoteright}UTR is necessary for modulating spontaneous neurotransmission in an activity-dependent manner, but not for viability. These data argue that regulation of CaMKII localization and levels by local transcriptional processes is conserved. This is the first demonstration of distinct functions for DrosophilaCaMKII mRNA variants.</p>
},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.1313-17.2017},
	author = {Kuklin, Elena A and Alkins, Stephen and Bakthavachalu, Baskar and Genco, Maria C and Sudhakaran, Indulekha and Raghavan, K Vijay and Ramaswami, Mani and Griffith, Leslie C}
}
