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.
Kita
Shunbun
S
Pharmaceutical Research Division, Pharmacology Research Laboratories I, Takeda Pharmaceutical Company Ltd, Yodogawa-ku, Osaka 532-8686, Japan.
Nishizawa
Hitoshi
H
Okuno
Yosuke
Y
Tanaka
Masaki
M
Yasui
Atsutaka
A
Matsuda
Morihiro
M
Yamada
Yukio
Y
Shimomura
Iichiro
I
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism*; D011485:Protein Binding; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism*
D009124:Muscle Proteins; C498449:Ostn protein, mouse; D014157:Transcription Factors; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C