|ZFIN ID: ZDB-PUB-080422-9|
The calcium channel beta2 (CACNB2) subunit repertoire in teleosts
Ebert, A.M., McAnelly, C.A., Srinivasan, A., Mueller, R.L., Garrity, D.B., and Garrity, D.M.
|Source:||BMC Molecular Biology 9(1): 38 (Journal)|
|Registered Authors:||Garrity, Deborah, Srinivasan, Ashok|
|PubMed:||18419826 Full text @ BMC Mol. Biol.|
Ebert, A.M., McAnelly, C.A., Srinivasan, A., Mueller, R.L., Garrity, D.B., and Garrity, D.M. (2008) The calcium channel beta2 (CACNB2) subunit repertoire in teleosts. BMC Molecular Biology. 9(1):38.
ABSTRACTBACKGROUND: Cardiomyocyte contraction is initiated by influx of extracellular calcium through voltage-gated calcium channels. These oligomeric channels utilize auxiliary beta subunits to chaperone the pore-forming alpha subunit to the plasma membrane, and to modulate channel electrophysiology. Several beta subunit family members are detected by RT-PCR in the embryonic heart. Null mutations in mouse beta 2, but not in the other three beta family members, are embryonic lethal at E10.5 due to defects in cardiac contractility . However, a drawback of the mouse model is that embryonic heart rhythm is difficult to study in live embryos due to their intra-uterine development. Moreover, phenotypes may be obscured by secondary effects of hypoxia. As a first step towards developing a model for contributions of beta subunits to the onset of embryonic heart rhythm, we characterized the structure and expression of beta 2 subunits in zebrafish and pufferfish. RESULTS: Cloning of two zebrafish beta 2 subunit genes (beta 2.1 and beta 2.2) indicated they are membrane-associated guanylate kinase (MAGUK)-family genes. Zebrafish beta genes show high conservation with mammals within the SH3 and guanylate kinase domains that comprise the core of MAGUK proteins, but beta 2.2 is much more divergent in sequence than beta 2.1. Alternative splicing occurs at the N-terminus and within the internal HOOK domain. In both beta 2 genes, alternative short ATG-containing first exons are separated by some of the largest introns in the genome, suggesting that individual transcript variants could be subject to independent cis-regulatory control. In the Tetraodon nigrovidis and Fugu rubripes genomes, we identified single beta 2 subunit gene loci. Comparative analysis of the zebrafish, pufferfish and human beta 2 loci indicates that the short 5 prime exon sequences are highly conserved. A subset of 5 prime exons appear to be unique to teleost genomes, while others are shared with mammals. Alternative splicing is under temporal and spatial regulation in both embryo and adult. Moreover, a different subset of beta 2 splice isoforms is detected in the embryonic heart compared to the adult. CONCLUSIONS: These studies refine our understanding of beta 2 subunit diversity arising from alternative splicing, and provide the groundwork for functional analysis of beta 2 subunit diversity in the embryonic heart.