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Specific Deletion of the FHA Domain Containing SLMAP3 Isoform in Postnatal Myocardium Has No Impact on Structure or Function

1
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
2
Health Canada, 414 Cooper St, Ottawa, ON K1A 0L4, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Argelia Medeiros-Domingo
Cardiogenetics 2021, 11(4), 164-184; https://doi.org/10.3390/cardiogenetics11040018
Received: 31 August 2021 / Revised: 23 September 2021 / Accepted: 29 September 2021 / Published: 4 October 2021
(This article belongs to the Section Molecular Genetics)
Sarcolemmal membrane-associated proteins (SLMAPs) belong to the superfamily of tail-anchored membrane proteins known to regulate diverse biological processes, including protein trafficking 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 defined as SLMAP1 (~35 kDa), SLMAP2 (~45 kDa) and SLMAP3 (~80–95 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-flox system to target the SLMAP gene, we specifically 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 deficiency revealed no significant changes to heart structure or function in young or aged mice without or with isoproterenol-induced stress. SLMAP3-deficient 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. View Full-Text
Keywords: SLMAP; αMHC-MerCreMer; postnatal myocardium; fork-head associated (FHA); Hippo signaling; sodium channel (Nav1.5) SLMAP; αMHC-MerCreMer; postnatal myocardium; fork-head associated (FHA); Hippo signaling; sodium channel (Nav1.5)
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MDPI and ACS Style

Rehmani, T.; Mlynarova, J.; Byers, J.; Salih, M.; Tuana, B.S. Specific Deletion of the FHA Domain Containing SLMAP3 Isoform in Postnatal Myocardium Has No Impact on Structure or Function. Cardiogenetics 2021, 11, 164-184. https://doi.org/10.3390/cardiogenetics11040018

AMA Style

Rehmani T, Mlynarova J, Byers J, Salih M, Tuana BS. Specific Deletion of the FHA Domain Containing SLMAP3 Isoform in Postnatal Myocardium Has No Impact on Structure or Function. Cardiogenetics. 2021; 11(4):164-184. https://doi.org/10.3390/cardiogenetics11040018

Chicago/Turabian Style

Rehmani, Taha, Jana Mlynarova, Joseph Byers, Maysoon Salih, and Balwant S. Tuana 2021. "Specific Deletion of the FHA Domain Containing SLMAP3 Isoform in Postnatal Myocardium Has No Impact on Structure or Function" Cardiogenetics 11, no. 4: 164-184. https://doi.org/10.3390/cardiogenetics11040018

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