Academic Journal
Isoform-specific subcellular localization and function of protein kinase A identified by mosaic imaging of mouse brain
| Title: | Isoform-specific subcellular localization and function of protein kinase A identified by mosaic imaging of mouse brain |
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| Authors: | Ronit Ilouz, Varda Lev-Ram, Eric A Bushong, Travis L Stiles, Dinorah Friedmann-Morvinski, Christopher Douglas, Jeffrey L Goldberg, Mark H Ellisman, Susan S Taylor |
| Source: | eLife, Vol 6 (2017) |
| Publisher Information: | eLife Sciences Publications Ltd, 2017. |
| Publication Year: | 2017 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | protein kinases, cellular and subcellular localization, Immunohistochemical mouse brain images, correlated light and electron microscopy, High resolution large scale images, PKA regulatory subunits, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | Protein kinase A (PKA) plays critical roles in neuronal function that are mediated by different regulatory (R) subunits. Deficiency in either the RIβ or the RIIβ subunit results in distinct neuronal phenotypes. Although RIβ contributes to synaptic plasticity, it is the least studied isoform. Using isoform-specific antibodies, we generated high-resolution large-scale immunohistochemical mosaic images of mouse brain that provided global views of several brain regions, including the hippocampus and cerebellum. The isoforms concentrate in discrete brain regions, and we were able to zoom-in to show distinct patterns of subcellular localization. RIβ is enriched in dendrites and co-localizes with MAP2, whereas RIIβ is concentrated in axons. Using correlated light and electron microscopy, we confirmed the mitochondrial and nuclear localization of RIβ in cultured neurons. To show the functional significance of nuclear localization, we demonstrated that downregulation of RIβ, but not of RIIβ, decreased CREB phosphorylation. Our study reveals how PKA isoform specificity is defined by precise localization. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/17681; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.17681 |
| Access URL: | https://doaj.org/article/9a4a23659ff14badb4cf350db9d9a487 |
| Accession Number: | edsdoj.9a4a23659ff14badb4cf350db9d9a487 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.17681 |
| Published in: | eLife |
| Language: | English |