| First Author | Pinter K | Year | 2012 |
| Journal | J Mol Cell Cardiol | Volume | 53 |
| Issue | 3 | Pages | 342-9 |
| PubMed ID | 22683324 | Mgi Jnum | J:186631 |
| Mgi Id | MGI:5432823 | Doi | 10.1016/j.yjmcc.2012.05.017 |
| Citation | Pinter K, et al. (2012) Embryonic expression of AMPK gamma subunits and the identification of a novel gamma2 transcript variant in adult heart. J Mol Cell Cardiol 53(3):342-9 |
| abstractText | AMP-activated protein kinase (AMPK), the key sensor and regulator of cellular energy status, is a heterotrimeric enzyme with multiple isoforms for each subunit (alpha1/alpha 2; beta1/beta2; gamma1/gamma2/gamma3). Mutations in PRKAG2, which encodes the gamma2 regulatory subunit, cause a cardiomyopathy characterized by hypertrophy and conduction abnormalities. The two reported PRKAG2 transcript variants, gamma2-short and gamma2-long (encoding 328 and 569 amino acids respectively), are both widely expressed in adult tissues. We show that both gamma2 variants are also expressed during cardiogenesis in mouse embryos; expression of the gamma3 isoform was also detected unexpectedly at this stage. As neither gamma2 transcript is cardiac specific nor differentially expressed during embryogenesis, it is paradoxical that the disease is largely restricted to the heart. However, a recently annotated gamma2 transcript, termed gamma2-3B as transcription starts at an alternative exon 3b, has been identified; it is spliced in-frame to exon 4 thus generating a protein of 443 residues in mouse with the first 32 residues being unique. It is increasingly expressed in the developing mouse heart and quantitative PCR analysis established that gamma2-3B is the major PRKAG2 transcript (~60%) in human heart. Antibody against the novel N-terminal sequence showed that gamma2-3B is predominantly expressed in the heart where it is the most abundant gamma2 protein. The abundance of gamma2-3B and its tissue specificity indicate that gamma2-3B may have non-redundant role in the heart and hence mediate the predominantly cardiac phenotype caused by PRKAG2 mutations. |
