Analysis of the CaMKII? and ? splice-variant distribution among brain regions reveals isoform-specific differences in holoenzyme formation.

ABSTRACT: Four CaMKII isoforms are encoded by distinct genes, and alternative splicing within the variable linker-region generates additional diversity. The ? and ? isoforms are largely brain-specific, where they mediate synaptic functions underlying learning, memory and cognition. Here, we determined the ? and ? splice-variant distribution among different mouse brain regions. Surprisingly, the nuclear variant ?B was detected in all regions, and even dominated in hypothalamus and brain stem. For CaMKII?, 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 CaMKII? gene lacks exon v3N that encodes the nuclear localization signal in ?B, but contains three exons not found in the CaMKII? gene (exons v1, v4, v5). While skipping of exons v1 and/or v5 generated the minor splice-variants ?', ?e and ?e', essentially all transcripts contained exon v4. However, we instead detected another minor splice-variant (now termed ?H), which lacks part of the hub domain that mediates formation of CaMKII holoenzymes. Surprisingly, in an optogenetic cellular assay of protein interactions, CaMKII?H was impaired for binding to the ? hub domain, but still bound CaMKII?. This provides the first indication for isoform-specific differences in holoenzyme formation.

SUBMITTER: Cook SG 

PROVIDER: S-EPMC5882894 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature