Browsing by keyword "local translation"
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Exosomes go with the WntExosomes, small secreted microvesicles, are implicated in intercellular communication in diverse cell types, transporting protein, lipid and nucleic acid cargo that impact the physiology of recipient cells. Besides the signaling function of exosomes they also serve as a mechanism to dispose obsolete cellular material. Particularly exciting is the involvement of exosomal communication in the nervous system, as this has important implications for brain development and function. The properties of exosomes are also beginning to entice the biomedical community since they represent potentially novel avenues for the targeted delivery of customized exosome cargo, such as miRNAs, during disease. Our findings implicating exosomes in trans-synaptic communication emerged from the serendipitous observation that at the Drosophila larval neuromuscular junction (NMJ) the release of a signaling molecule, Wnt1/Wingless (Wg) and its binding partner Evenness Interrupted (Evi)/Wntless (Wls)/Sprint (Srt), were released by motorneurons in association with vesicles, which we postulated to be exosomes. In our most recent paper using in vivo analysis at the Drosophila NMJ as well as in cultured insect cells we formally demonstrate that Evi rides in exosomes that are released to the extracellular space and identify some of the players involved in their release. In addition, a proteomic analysis of exosomes highlights novel potential function of exosomes.
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Regulation of Local Translation, Synaptic Plasticity, and Cognitive Function by CNOT7Local translation of mRNAs in dendrites is vital for synaptic plasticity and learning and memory. Tight regulation of this translation is key to preventing neurological disorders resulting from aberrant local translation. Here we find that CNOT7, the major deadenylase in eukaryotic cells, takes on the distinct role of regulating local translation in the hippocampus. Depletion of CNOT7 from cultured neurons affects the poly(A) state, localization, and translation of dendritic mRNAs while having little effect on the global neuronal mRNA population. Following synaptic activity, CNOT7 is rapidly degraded resulting in polyadenylation and a change in the localization of its target mRNAs. We find that this degradation of CNOT7 is essential for synaptic plasticity to occur as keeping CNOT7 levels high prevents these changes. This regulation of dendritic mRNAs by CNOT7 is necessary for normal neuronal function in vivo, as depletion of CNOT7 also disrupts learning and memory in mice. We utilized deep sequencing to identify the neuronal mRNAs whose poly(A) state is governed by CNOT7. Interestingly these mRNAs can be separated into two distinct populations: ones that gain a poly(A) tail following CNOT7 depletion and ones that surprisingly lose their poly(A) tail following CNOT7 depletion. These two populations are also distinct based on the lengths of their 3’ UTRs and their codon usage, suggesting that these key features may dictate how CNOT7 acts on its target mRNAs. This work reveals a central role for CNOT7 in the hippocampus where it governs local translation and higher cognitive function.
