TY - JOUR
T1 - Astrocytes locally translate transcripts in their peripheral processes
AU - Sakers, Kristina
AU - Lake, Allison M.
AU - Khazanchi, Rohan
AU - Ouwenga, Rebecca
AU - Vasek, Michael J.
AU - Dani, Adish
AU - Dougherty, Joseph D.
N1 - Funding Information:
This work was supported by the Children's Discovery Institute (CDI) (MD-II-2013-269), the NIH (DA038458-01, MH099798-01, NS086741, 5T32 GM081739, T32 GM008151), and a CDI microgrant (CDI-CORE-2015-505), the Foundation for Barnes-Jewish Hospital (3770), the Hope Center by the Viral Vectors Core, and the Genome Technology Resource Center at Washington University in St. Louis (NIH P30CA91842 and UL1TR000448).
PY - 2017/5/9
Y1 - 2017/5/9
N2 - Local translation in neuronal processes is key to the alteration of synaptic strength necessary for long-term potentiation, learning, and memory. Here, we present evidence that regulated de novo protein synthesis occurs within distal, perisynaptic astrocyte processes. Astrocyte ribosomal proteins are found adjacent to synapses in vivo, and immunofluorescent detection of peptide elongation in acute slices demonstrates robust translation in distal processes. We have also developed a biochemical approach to define candidate transcripts that are locally translated in astrocyte processes. Computational analyses indicate that astrocyte-localized translation is both sequence-dependent and enriched for particular biological functions, such as fatty acid synthesis, and for pathways consistent with known roles for astrocyte processes, such as GABA and glutamate metabolism. These transcripts also include glial regulators of synaptic refinement, such as Sparc. Finally, the transcripts contain a disproportionate amount of a binding motif for the quaking RNA binding protein, a sequence we show can significantly regulate mRNA localization and translation in the astrocytes. Overall, our observations raise the possibility that local production of astrocyte proteins may support microscale alterations of adjacent synapses.
AB - Local translation in neuronal processes is key to the alteration of synaptic strength necessary for long-term potentiation, learning, and memory. Here, we present evidence that regulated de novo protein synthesis occurs within distal, perisynaptic astrocyte processes. Astrocyte ribosomal proteins are found adjacent to synapses in vivo, and immunofluorescent detection of peptide elongation in acute slices demonstrates robust translation in distal processes. We have also developed a biochemical approach to define candidate transcripts that are locally translated in astrocyte processes. Computational analyses indicate that astrocyte-localized translation is both sequence-dependent and enriched for particular biological functions, such as fatty acid synthesis, and for pathways consistent with known roles for astrocyte processes, such as GABA and glutamate metabolism. These transcripts also include glial regulators of synaptic refinement, such as Sparc. Finally, the transcripts contain a disproportionate amount of a binding motif for the quaking RNA binding protein, a sequence we show can significantly regulate mRNA localization and translation in the astrocytes. Overall, our observations raise the possibility that local production of astrocyte proteins may support microscale alterations of adjacent synapses.
KW - Astrocyte
KW - Local translation
KW - RNA-sequencing
KW - Synapse
KW - TRAP
UR - http://www.scopus.com/inward/record.url?scp=85019141725&partnerID=8YFLogxK
U2 - 10.1073/pnas.1617782114
DO - 10.1073/pnas.1617782114
M3 - Article
C2 - 28439016
AN - SCOPUS:85019141725
SN - 0027-8424
VL - 114
SP - E3830-E3838
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -