Competitive binding of musclin to natriuretic peptide receptor 3 with atrial natriuretic peptide.

Musclin is a novel skeletal muscle-derived secretory factor that was isolated by our group. Musclin contains a region homologous to natriuretic peptides (NPs). This study investigated the interaction between musclin and NP receptors (NPRs). Musclin specifically bound to NPR3, but not to NPR1 or NPR2. Musclin and atrial natriuretic peptide (ANP) competed for binding to NPR3. We conducted binding assays using various synthetic musclin peptides and mutant musclin proteins. The first NP-homologous region in musclin ((88)LDRL(91)) and the second homologous region ((117)MDRI(120)) were responsible cooperatively for high-affinity binding to NPR3. The first NP-homologous region was more importantly associated with binding to NPR3, than the second homologous region. The competitive nature of musclin with ANP for the natriuretic clearance receptor NPR3 was also confirmed in vivo. We conclude that musclin binds to NPR3 competitively with ANP and may affect ANP concentrations in a local or systemic manner.

[1]  C. Lanctôt,et al.  Osteocrin Is a Specific Ligand of the Natriuretic Peptide Clearance Receptor That Modulates Bone Growth* , 2007, Journal of Biological Chemistry.

[2]  M. Matsuda,et al.  Foxo1 represses expression of musclin, a skeletal muscle-derived secretory factor. , 2007, Biochemical and biophysical research communications.

[3]  J. Eckel,et al.  The adipocyte–myocyte axis in insulin resistance , 2006, Trends in Endocrinology & Metabolism.

[4]  D. Dickey,et al.  Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. , 2006, Endocrine reviews.

[5]  J. Jordan,et al.  Lipid mobilization with physiological atrial natriuretic peptide concentrations in humans. , 2005, The Journal of clinical endocrinology and metabolism.

[6]  M. Matsuda,et al.  Musclin, a Novel Skeletal Muscle-derived Secretory Factor* , 2004, Journal of Biological Chemistry.

[7]  C. Holding,et al.  Insulin-like growth factor-binding protein 5 (Igfbp5) compromises survival, growth, muscle development, and fertility in mice , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  C. Lanctôt,et al.  Osteocrin, a Novel Bone-specific Secreted Protein That Modulates the Osteoblast Phenotype* , 2003, Journal of Biological Chemistry.

[9]  M. Berlan,et al.  Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women , 2002, International Journal of Obesity.

[10]  Antonio Musarò,et al.  Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle , 2001, Nature Genetics.

[11]  R. Sarzani,et al.  Low calorie diet enhances renal, hemodynamic, and humoral effects of exogenous atrial natriuretic peptide in obese hypertensives. , 1999, Hypertension.

[12]  S. Cinti,et al.  Fasting inhibits natriuretic peptides clearance receptor expression in rat adipose tissue , 1995, Journal of hypertension.

[13]  J. R. Jewett,et al.  Extracellular domain-IgG fusion proteins for three human natriuretic peptide receptors. Hormone pharmacology and application to solid phase screening of synthetic peptide antisera. , 1991, The Journal of biological chemistry.

[14]  J. Lewicki,et al.  Clearance function of type C receptors of atrial natriuretic factor in rats. , 1989, The American journal of physiology.

[15]  J. Lewicki,et al.  Physiological role of silent receptors of atrial natriuretic factor. , 1987, Science.

[16]  M. Sigler.  The mechanism of the natriuresis of fasting. , 1975, The Journal of clinical investigation.