We are interested in studying the role of the protein Melusin in cardioprotection. Melusin is an intracellular muscle specific protein, selectively expressed in skeletal and cardiac muscles. It functions as a mechanical stretch sensor in muscle cells thanks to its ability to bind the cytoplasmic region of beta 1 integrin and to activate MAPK and PI3K/AKT intracellular signaling, leading to cardiomyocyte hypertrophy and survival1, 2, 3. Melusin overexpression in cardiomyocytes improves myocardial function in different stress conditions, like pressure overload, myocardial infarction and ischemia/reperfusion injury2, 4, 5.
Melusin belongs to the CHORD containing protein family, since it contains two CHORD (Cysteine and Histidine rich) domains located at its N-terminal. These domains are phylogenetically conserved from plants to mammals6 and mediate the interaction with other proteins, among them the chaperone protein HSP907. Melusin is also characterized by the presence of a CS domain (typical of CHORD and SGT1 proteins)6, able to interact whit the cytoplasmic region of the beta 1 integrin. At the C-terminal end is located a Ca++ binding domain.
The known Melusin binding partners are listed in the table below.
TH: two hybrid
PD: Pull down
SPR: surface plasmon resonance
ACC: Affinity column chromatrography
Melusin promotes the activation of intracellular signaling inside the cardiomyocytes in response to mechanical overload. It forms complexes with the beta 1 integrin, the Focal Adhesion Kinase, the MAPK scaffold protein IQGAP1, RAF, MEK, ERK, PI3K and AKT. It also binds the chaperone protein HSP90, that is required for the activation of many of the signaling molecules listed above. We suspect that Melusin mediates the formation of a supramolecular complex to activate specific compensatory signals in response to mechanical stress.
THANKS TO GUIDO!
Guido headed the research on Melusin for almost 20 years and thanks to his enthusiasm and scientific abilities many features of Melusin have been unveiled. We intend to go on with the same passion and curiosity.