Melusin Is a New Muscle-specific Interactor for β1Integrin Cytoplasmic Domain

Brancaccio, Mara; Guazzone, Simona; Menini, Nadia; Sibona, Emanuele; Hirsch, Emilio; Andrea, Marco De; Rocchi, Mariano; Altruda, Fiorella; Tarone, Guido; Silengo, Lorenzo

doi:10.1074/jbc.274.41.29282

Cited by 101 publications

(101 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CD9 and FRZB are positive regulators of ITGB1BP2 gene expression and ITGB1BP2 is a negative regulator of FRZB gene expression in myotubes As melusin and CD9 interact with integrin β1 ( Refs 12,14,15,16), and the expression of ITGB1BP2, CD9 and FRZB genes is upregulated in calpain 3-deficient patients, siRNA experiments were carried out in myotubes, to find out whether there was any coordinated regulation of these genes. At 48 h after treatment with CD9 siRNA, cultures showed markedly less CD9 mRNA (90%) than in those treated with scrambled LGMD2A CONTROL LGMD2A 25µM 25µM…”

Section: Frzb and Melusin Overexpressed In Lgmd2amentioning

confidence: 99%

FRZB and melusin, overexpressed in LGMD2A, regulate integrin β1D isoform replacement altering myoblast fusion and the integrin-signalling pathway

Jaka

Casas-Fraile

Azpitarte

et al. 2017

Expert Rev. Mol. Med.

View full text Add to dashboard Cite

Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterised by muscle wasting and progressive degeneration of proximal muscles because of mutations in the CAPN3 gene. However, the underlying pathophysiological mechanisms of muscle degeneration are still not well understood. The objective of this study was to assess the relevance of genes with differential expression in the muscle of LGMD2A patients. For this purpose, we analysed their in vitro expression in primary cultures of human myoblasts and myotubes. Abnormal fusion was observed in the myotubes of these patients, which may be explained by the lack of physiological replacement of integrin β1D. Owing to this observation, we focused on deregulated genes coding proteins that directly interact with integrin, ITGB1BP2 and CD9, as well as FRZB gene, because of its in vitro upregulation in myotubes. Silencing studies established that these genes are closely regulated, CD9 and FRZB being positive regulators of the expression of ITGB1BP2, and in turn, this gene being a negative regulator of the expression of FRZB. Interestingly, we observed that FRZB regulates integrin β1D expression, its silencing increasing integrin β1D expression to levels similar to those in controls. Finally, the administration of LiCl, an enhancer of the Wnt-signalling pathway showed similar experimentally beneficial effects, suggesting FRZB silencing or LiCl administration as potential therapeutic targets, though further studies are required.

show abstract

Section: Frzb and Melusin Overexpressed In Lgmd2amentioning

confidence: 99%

FRZB and melusin, overexpressed in LGMD2A, regulate integrin β1D isoform replacement altering myoblast fusion and the integrin-signalling pathway

Jaka

Casas-Fraile

Azpitarte

et al. 2017

Expert Rev. Mol. Med.

View full text Add to dashboard Cite

show abstract

“…Melusin is a striated muscle-specific, cysteine-rich, 38-kDa protein that is also localized to cardiomyocyte costameres (16). The COOH-terminal tail region of the molecule directly interacts with the cytoplasmic tail of ␤ 1 -integrins, where it appears to function as part of the mechanosensory apparatus that transduces increased pressure (produced by aortic constriction) to gene expression changes resulting in the progression of left ventricular hypertrophy to heart failure (15,26).…”

Section: Other Muscle-specific Integrin-binding Proteins and Cardiomentioning

confidence: 99%

Costameres, focal adhesions, and cardiomyocyte mechanotransduction

Samarel¹

2005

American Journal of Physiology-Heart and Circulatory Physiology

252

201

View full text Add to dashboard Cite

Samarel, Allen M. Costameres, focal adhesions, and cardiomyocyte mechanotransduction. Am J Physiol Heart Circ Physiol 289: H2291-H2301, 2005; doi: 10.1152/ajpheart.00749.2005.-Mechanotransduction refers to the cellular mechanisms by which load-bearing cells sense physical forces, transduce the forces into biochemical signals, and generate appropriate responses leading to alterations in cellular structure and function. This process affects the beat-to-beat regulation of cardiac performance but also affects the proliferation, differentiation, growth, and survival of the cellular components that comprise the human myocardium. This review focuses on the experimental evidence indicating that the costamere and its structurally related structure the focal adhesion complex are critical cytoskeletal elements involved in cardiomyocyte mechanotransduction. Biochemical signals originating from the extracellular matrix-integrin-costameric protein complex share many common features with those signals generated by growth factor receptors. The roles of key regulatory kinases and other muscle-specific proteins involved in mechanotransduction and growth factor signaling are discussed, and issues requiring further study in this field are outlined.focal adhesion kinase; proline-rich tyrosine kinase 2; integrin-linked kinase; protein kinase C; signal transduction; heart THE PROCESS OF MECHANOTRANSDUCTION refers to the cellular mechanisms by which load-bearing cells sense physical forces, transduce the forces into biochemical signals, and generate appropriate responses leading to alterations in cellular structure and function. Physical forces encountered by living cells include membrane stretch, gain and loss of adhesion, and compression due to an increase in pressure. The signal transduction pathways that are activated in response to mechanical forces include many unique components, as well as elements shared by other signaling pathways. Mechanotransduction in cardiomyocytes is particularly complex, in that individual muscle cells both respond to externally applied mechanical forces as well as generate internal loads that are transmitted to adjacent cells and their surrounding extracellular matrix (ECM). Mechanotransduction in both atrial and ventricular cardiomyocytes affects the beat-to-beat regulation of cardiac performance but also profoundly affects the proliferation, differentiation, growth, and survival of the cellular components that comprise the human myocardium. Understanding the cellular and molecular basis for mechanotransduction is therefore important to our overall understanding of cardiac structure and function in the normal and diseased heart.Observational studies conducted during the 1970s addressing the hypertrophic growth response of human myocardium to pathological changes in systolic and diastolic wall stress (42) fostered the development of experimental model systems with which to explore cardiomyocyte mechanotransduction in vivo and in vitro. These model systems now span the breadth of experimental cardiology...

show abstract

“…These include calreticulin and FAK, as well as melusin and muscle integrin-binding protein (MIBP), both of which are preferentially expressed in muscle. [35][36][37][38] Additionally, integrin cytoplasmic tails bind directly to components of the cytoskeleton such as talin and ␣-actinin. Ultimately, signaling from the integrins may influence pathways through which other cellular effectors (such as growth factors) may also signal, including those requiring Akt, Raf, phosphoinositide 3-kinase (PI3-K), or mitogen-activated protein kinases (MAPKs)/extracellular signal-regulated kinases (ERKs).…”

Section: Integrin Function and Expressionmentioning

confidence: 99%

Integrins and the Myocardium

Ross

Borg

2001

Circulation Research

396

279

View full text Add to dashboard Cite

Abstract-Extracellular matrix provides a structural, chemical, and mechanical substrate that is essential in cardiac development, growth, and responses to pathophysiological signals. Transmembrane receptors termed integrins provide a dynamic interaction of environmental cues and intracellular events. Integrins orchestrate multiple functions in the intact organism including organogenesis, regulation of gene expression, cell proliferation, differentiation, migration, and death. They are expressed in all cellular components of the cardiovascular system, including the vasculature, blood, cardiac myocytes and nonmuscle cardiac cells. The focus of this review will be on the role of integrins in the myocardium. We will provide background on integrin structure and function, discuss how the expression of integrins is critical to the form and function of the developing and postnatal myocardium, and review the known data on integrins as signaling molecules in the heart. Finally, we will offer insights to the future research directions into this important family of extracellular matrix receptors in the myocardium. Key Words: integrin Ⅲ myocardium Ⅲ extracellular matrix E xtracellular matrix (ECM) provides a structural, chemical, and mechanical substrate that is essential in cardiac development, growth, and responses to pathophysiological signals. Transmembrane receptors termed integrins provide a dynamic interaction of environmental cues and intracellular events. [1][2][3] Integrins orchestrate multiple functions in the intact organism including organogenesis, regulation of gene expression, cell proliferation, differentiation, migration, and death. They are expressed in all cellular components of the cardiovascular system, including the vasculature, blood, cardiac myocytes, and nonmuscle cardiac cells. The focus of this review will be on the role of integrins in the myocardium, because their function in the vasculature and platelets has been recently reviewed. 4,5 We will discuss how the expression of integrins is critical to the form and function of the myocardium, evaluate potential mechanisms of action of the integrins in the regulation of these processes, and offer insights to the future research directions into this important family of ECM receptors in the myocardium. Integrin StructureIntegrins are noncovalently associated heterodimeric transmembrane receptors composed of ␣ and ␤ subunits, with ␣ subunits ranging from 120 to 180 kDa whereas ␤ subunits are 90 to 110 kDa. 3,6 Historically, integrins were identified based on an initial series of experiments suggesting a physical association between fibronectin and the intracellular cytoskeleton. 7 Subsequently, studies were published from several laboratories that (1) identified glycoproteins having characteristics of membrane proteins, and (2) showed that antibodies which recognized these proteins could inhibit cellular adhesion. 8 -12 These observations led to the cloning of chick fibroblast cDNAs that encoded for a molecule involved in transmembrane linkage between f...

show abstract

Melusin Is a New Muscle-specific Interactor for β1Integrin Cytoplasmic Domain

Abstract: Here we describe the isolation and partial characterization of a new muscle-specific protein (Melusin) which interacts with the integrin cytoplasmic domain. The cDNA encoding Melusin was isolated in a two-hybrid screening of a rat neonatal heart library using

Cited by 101 publications

References 39 publications

FRZB and melusin, overexpressed in LGMD2A, regulate integrin β1D isoform replacement altering myoblast fusion and the integrin-signalling pathway

FRZB and melusin, overexpressed in LGMD2A, regulate integrin β1D isoform replacement altering myoblast fusion and the integrin-signalling pathway

Costameres, focal adhesions, and cardiomyocyte mechanotransduction

Integrins and the Myocardium

Contact Info

Product

Resources

About