Germline deletion of FAK-related non-kinase delays post-natal cardiomyocyte mitotic arrest.

Journal of Molecular and Cellular Cardiology
Thomas J O'NeillJoan M Taylor

Abstract

The cardiomyocyte phenotypic switch from a proliferative to terminally differentiated state impacts normal heart development and pathologic myocardial remodeling, yet the signaling mechanisms that regulate this vital process are incompletely understood. Studies from our lab and others indicate that focal adhesion kinase (FAK) is a critical regulator of cardiac growth and remodeling and we found that expression of the endogenous FAK inhibitor, FAK-related non kinase (FRNK) coincided with postnatal cardiomyocyte arrest. Mis-expression of FRNK in the embryonic heart led to pre-term lethality associated with reduced cardiomyocyte proliferation and led us to speculate that the postnatal FRNK surge might be required to promote quiescence in this growth promoting environment. Herein, we provide strong evidence that endogenous FRNK contributes to post-mitotic arrest. Depletion of FRNK promoted DNA synthesis in post-natal day (P) 10 hearts accompanied by a transient increase in DNA content and multi-nucleation by P14, indicative of DNA replication without cell division. Interestingly, a reduction in tri- and tetra-nucleated cardiomyocytes, concomitant with an increase in bi-nucleated cells by P21, indicated the possibility that FRNK-dep...Continue Reading

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Citations

Mar 14, 2014·Cardiovascular Research·Serena Zacchigna, Mauro Giacca
Oct 19, 2017·Scientific Reports·Salma E Jiménez-BadilloJavier Hernández-Sánchez
Aug 19, 2017·Journal of Applied Physiology·Wataru KimuraHesham A Sadek

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