Local translation provides the asymmetric distribution of CaMKII required for associative memory formation.

Autor: Chen N; Department of Biology, Volen National Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454-9110, USA., Zhang Y; Department of Biology, Volen National Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454-9110, USA., Adel M; Department of Biology, Volen National Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454-9110, USA., Kuklin EA; Department of Biology, Volen National Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454-9110, USA., Reed ML; Department of Biology, Volen National Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454-9110, USA., Mardovin JD; Department of Biology, Volen National Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454-9110, USA., Bakthavachalu B; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore 560065, India; School of Basic Science, Indian Institute of Technology Mandi, Mandi, India., VijayRaghavan K; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore 560065, India; School of Basic Science, Indian Institute of Technology Mandi, Mandi, India., Ramaswami M; Trinity College Institute of Neuroscience, School of Genetics and Microbiology and School of Natural Sciences, Trinity College Dublin, Dublin 2, Ireland; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore 560065, India; School of Basic Science, Indian Institute of Technology Mandi, Mandi, India., Griffith LC; Department of Biology, Volen National Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454-9110, USA. Electronic address: griffith@brandeis.edu.
Jazyk: angličtina
Zdroj: Current biology : CB [Curr Biol] 2022 Jun 20; Vol. 32 (12), pp. 2730-2738.e5. Date of Electronic Publication: 2022 May 10.
DOI: 10.1016/j.cub.2022.04.047
Abstrakt: 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 2+ /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.
Competing Interests: Declaration of interests The authors declare no competing interests.
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Databáze: MEDLINE