Analysis of the CaMKIIα and ß splice-variant distribution among brain regions reveals isoform-specific differences in holoenzyme formation.
Sci Rep
; 8(1): 5448, 2018 04 03.
Article
em En
| MEDLINE
| ID: mdl-29615706
ABSTRACT
Four CaMKII isoforms are encoded by distinct genes, and alternative splicing within the variable linker-region generates additional diversity. The α and ß isoforms are largely brain-specific, where they mediate synaptic functions underlying learning, memory and cognition. Here, we determined the α and ß splice-variant distribution among different mouse brain regions. Surprisingly, the nuclear variant αB was detected in all regions, and even dominated in hypothalamus and brain stem. For CaMKIIß, 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 CaMKIIß gene lacks exon v3N that encodes the nuclear localization signal in αB, but contains three exons not found in the CaMKIIα gene (exons v1, v4, v5). While skipping of exons v1 and/or v5 generated the minor splice-variants ß', ße and ße', essentially all transcripts contained exon v4. However, we instead detected another minor splice-variant (now termed ßH), which lacks part of the hub domain that mediates formation of CaMKII holoenzymes. Surprisingly, in an optogenetic cellular assay of protein interactions, CaMKIIßH was impaired for binding to the ß hub domain, but still bound CaMKIIα. This provides the first indication for isoform-specific differences in holoenzyme formation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Holoenzimas
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina
Limite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos