Abstract
Melusin is a chaperone protein selectively expressed in heart and skeletal muscles. Melusin expression levels correlate with cardiac function in pre-clinical models and in human patients with aortic stenosis. Indeed, previous studies in several animal models indicated that Melusin plays a broad cardioprotective role in different pathological conditions. Chaperone proteins, besides playing a role in protein folding, are also able to facilitate supramolecular complex formation and conformational changes due to activation/deactivation of signaling molecules. This role sets chaperone proteins as crucial regulators of intracellular signal transduction pathways. In particular Melusin activates AKT and ERK1/2 signaling, protects cardiomyocytes from apoptosis and induces a compensatory hypertrophic response in several pathological conditions. Therefore, selective delivery of the Melusin gene in heart via cardiotropic adenoviral associated virus serotype 9 (AAV9), may represent a new promising gene-therapy approach for different cardiac pathologies.
Highlights
Matteo Sorge and Mara Brancaccio *Besides playing a role in protein folding, are able to facilitate supramolecular complex formation and conformational changes due to activation/deactivation of signaling molecules
Mechanical stretch and humoral factors released in response to excessive workload activate signal transduction pathways (Tarone and Lembo, 2003) that need to be assisted by chaperones to properly sustain cell survival and induce cardiomyocyte hypertrophic growth
We demonstrated a role for the Focal adhesion kinase in activating Melusin-bound ERK1/2 in response to mechanical stretch (Sbroggiò et al, 2011a)
Summary
Besides playing a role in protein folding, are able to facilitate supramolecular complex formation and conformational changes due to activation/deactivation of signaling molecules. Mechanical stretch and humoral factors released in response to excessive workload activate signal transduction pathways (Tarone and Lembo, 2003) that need to be assisted by chaperones to properly sustain cell survival and induce cardiomyocyte hypertrophic growth. It is conceivable that Hsp plays multiple important roles in sustaining heart function upon stress adaptation, by inducing protein refolding, directing unfolded proteins to proteasome degradation, and assisting conformational changes in signal transduction molecules (Ficker et al, 2003; Kupatt et al, 2004; Tarone and Brancaccio, 2014; Parry et al, 2015).
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