| First Author | Rehmani T | Year | 2021 |
| Journal | Cardiogenetics | Volume | 11 |
| Pages | 164-184 | Mgi Jnum | J:350523 |
| Mgi Id | MGI:7663947 | Doi | 10.3390/cardiogenetics11040018 |
| Citation | Rehmani T, et al. (2021) Specific deletion of the FHA domain containing SLMAP3 isoform in postnatal myocardium has no impact on structure or function. Cardiogenetics 11:164-184 |
| abstractText | Sarcolemmal membrane-associated proteins (SLMAPs) belong to the superfamily of tail-anchored membrane proteins known to regulate diverse biological processes, including protein trafï¬cking and signal transduction. Mutations in SLMAP have been linked to Brugada and defective sodium channel Nav1.5 shuttling. The SLMAP gene is alternatively spliced to generate numerous isoforms, broadly deï¬ned as SLMAP1 (~35 kDa), SLMAP2 (~45 kDa) and SLMAP3 (~80â95 kDa), which are highly expressed in the myocardium. The SLMAP3 isoform exhibits ubiquitous expression carrying an FHA domain and is believed to negatively regulate Hippo signaling to dictate cell growth/death and differentiation. Using the αMHC-MerCreMer-ï¬ox system to target the SLMAP gene, we speciï¬cally deleted the SLMAP3 isoform in postnatal mouse hearts without any changes in the expression of SLMAP1/SLMAP2 isoforms. The in vivo analysis of mice with SLMAP3 cardiac deï¬ciency revealed no signiï¬cant changes to heart structure or function in young or aged mice with-out or with isoproterenol-induced stress. SLMAP3-deï¬cient hearts revealed no obvious differences in cardiac size, function or hypertrophic response. Further, the molecular analysis indicated that SLMAP3 loss had a minor impact on sodium channel (Nav1.5) expression without affecting cardiac electrophysiology in postnatal myocardium. Surprisingly, the loss of SLMAP3 did not impact Hippo signaling in postnatal myocardium. We conclude that the FHA domain-containing SLMAP3 isoform has no impact on Hippo signaling or sodium channels in postnatal myocardium, which is able to function and respond normally to stress in its absence. Whether SLMAP1/SMAP2 isoforms can compensate for the loss of SLMAP3 in the affairs of the postnatal heart remains to be determined. |
