Disease relevance of Itgb1bp2

• Melusin is a muscle specific protein required for heart hypertrophy in response to mechanical overload [1].
• Melusin-null mice showed normal cardiac structure and function in physiological conditions, but when subjected to pressure overload--a condition that induces a hypertrophic response in wild-type controls--they developed an abnormal cardiac remodeling that evolved into dilated cardiomyopathy and contractile dysfunction [2].
• After prolonged pressure overload (12 weeks), melusin overexpressing hearts underwent further hypertrophy retaining concentric LV remodeling and full contractile function, whereas wild-type LV showed pronounced chamber dilation with an impaired contractility [3].

High impact information on Itgb1bp2

• Melusin, a muscle-specific integrin beta1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload [2].
• Analysis of intracellular signaling events induced by pressure overload indicated that phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) was specifically blunted in melusin-null hearts [2].
• In contrast, the hypertrophic response was identical in wild-type and melusin-null mice after chronic administration of angiotensin II or phenylephrine at doses that do not increase blood pressure--that is, in the absence of cardiac biomechanical stress [2].
• By gene inactivation, we demonstrate here a crucial role of melusin, a muscle-specific protein that interacts with the integrin beta1 cytoplasmic domain, in the hypertrophic response to mechanical overload [2].
• Chp-1 and melusin, two CHORD containing proteins in vertebrates [1].

Biological context of Itgb1bp2

• While invertebrate genome contains only one gene coding for a chp-1 homolog, two genes coding for CHORD containing proteins (chp-1 and melusin) are present in vertebrates [1].
• Sequence analysis suggests that the muscle specific CHORD containing protein melusin originated by a gene duplication event during early chordate evolution [1].
• In addition, after 12 weeks of pressure overload LV of melusin overexpressing mice showed a very low level of cardiomyocyte apoptosis and stromal tissue deposition, as well as increased capillary density compared with wild-type [3].

Anatomical context of Itgb1bp2

• We have previously shown that genetic ablation of melusin, a muscle specific beta 1 integrin interacting protein, accelerates left ventricle (LV) dilation and heart failure in response to pressure overload [3].

Enzymatic interactions of Itgb1bp2

• Moreover, AKT, GSK3beta and ERK1/2 were hyper-phosphorylated on pressure overload in melusin overexpressing compared with wild-type mice [3].

Regulatory relationships of Itgb1bp2

• Analysis of signaling pathways indicated that melusin overexpression induced increased basal phosphorylation of GSK3beta and ERK1/2 [3].

Analytical, diagnostic and therapeutic context of Itgb1bp2

• Echocardiography analysis indicated that melusin over-expression induced a mild cardiac hypertrophy in basal conditions (30% increase in interventricular septum thickness) with no obvious structural and functional alterations [3].

References