| First Author | Cook SG | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 5448 |
| PubMed ID | 29615706 | Mgi Jnum | J:262849 |
| Mgi Id | MGI:6162948 | Doi | 10.1038/s41598-018-23779-4 |
| Citation | Cook SG, et al. (2018) Analysis of the CaMKIIalpha and beta splice-variant distribution among brain regions reveals isoform-specific differences in holoenzyme formation. Sci Rep 8(1):5448 |
| abstractText | Four CaMKII isoforms are encoded by distinct genes, and alternative splicing within the variable linker-region generates additional diversity. The alpha and beta isoforms are largely brain-specific, where they mediate synaptic functions underlying learning, memory and cognition. Here, we determined the alpha and beta splice-variant distribution among different mouse brain regions. Surprisingly, the nuclear variant alphaB was detected in all regions, and even dominated in hypothalamus and brain stem. For CaMKIIbeta, the full-length variant dominated in most regions (with higher amounts of minor variants again seen in hypothalamus and brain stem). The mammalian but not fish CaMKIIbeta gene lacks exon v3N that encodes the nuclear localization signal in alphaB, but contains three exons not found in the CaMKIIalpha gene (exons v1, v4, v5). While skipping of exons v1 and/or v5 generated the minor splice-variants beta', betae and betae', essentially all transcripts contained exon v4. However, we instead detected another minor splice-variant (now termed betaH), which lacks part of the hub domain that mediates formation of CaMKII holoenzymes. Surprisingly, in an optogenetic cellular assay of protein interactions, CaMKIIbetaH was impaired for binding to the beta hub domain, but still bound CaMKIIalpha. This provides the first indication for isoform-specific differences in holoenzyme formation. |
