β-Arrestin scaffolds and signaling elements essential for the obestatin/GPR39 system that determine the myogenic program in human myoblast cells.

Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE

Publication: Basel : Springer
Original Publication: Basel ; Boston : Birkhauser, c1997-

Arrestins/*physiology ; Ghrelin/*metabolism ; Muscle Development/*genetics ; Receptors, G-Protein-Coupled/*metabolism; Arrestins/chemistry ; Arrestins/genetics ; Arrestins/metabolism ; Cell Cycle ; Cell Differentiation ; Cell Proliferation ; Ghrelin/physiology ; Humans ; Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal/cytology ; Phosphorylation ; Receptors, G-Protein-Coupled/physiology ; Signal Transduction ; beta-Arrestin 1 ; beta-Arrestins

Obestatin/GPR39 signaling stimulates skeletal muscle repair by inducing the expansion of satellite stem cells as well as myofiber hypertrophy. Here, we describe that the obestatin/GPR39 system acts as autocrine/paracrine factor on human myogenesis. Obestatin regulated multiple steps of myogenesis: myoblast proliferation, cell cycle exit, differentiation and recruitment to fuse and form multinucleated hypertrophic myotubes. Obestatin-induced mitogenic action was mediated by ERK1/2 and JunD activity, being orchestrated by a G-dependent mechanism. At a later stage of myogenesis, scaffolding proteins β-arrestin 1 and 2 were essential for the activation of cell cycle exit and differentiation through the transactivation of the epidermal growth factor receptor (EGFR). Upon obestatin stimulus, β-arrestins are recruited to the membrane, where they functionally interact with GPR39 leading to Src activation and signalplex formation to EGFR transactivation by matrix metalloproteinases. This signalplex regulated the mitotic arrest by p21 and p57 expression and the mid- to late stages of differentiation through JNK/c-Jun, CAMKII, Akt and p38 pathways. This finding not only provides the first functional activity for β-arrestins in myogenesis but also identify potential targets for therapeutic approaches by triggering specific signaling arms of the GPR39 signaling involved in myogenesis.

Cell Stem Cell. 2012 May 4;10(5):515-9. (PMID: 22560075)
Annu Rev Pharmacol Toxicol. 2012;52:179-97. (PMID: 21942629)
Cell Metab. 2012 Aug 8;16(2):153-66. (PMID: 22795476)
Biochem J. 2013 Oct 15;455(2):169-77. (PMID: 23905709)
J Biol Chem. 2008 Jul 4;283(27):18852-60. (PMID: 18477563)
Mol Aspects Med. 2008 Oct;29(5):258-89. (PMID: 18762209)
J Cell Physiol. 2009 May;219(2):503-11. (PMID: 19142853)
J Endocrinol. 2011 Aug;210(2):R1-7. (PMID: 21690170)
Physiol Rev. 2013 Jan;93(1):23-67. (PMID: 23303905)
Dev Biol. 2004 Nov 15;275(2):375-88. (PMID: 15501225)
Biol Cell. 2008 Mar;100(3):189-99. (PMID: 17988214)
Endocr Relat Cancer. 2009 Jun;16(2):599-611. (PMID: 19153210)
Nature. 2005 Jan 20;433(7023):317-22. (PMID: 15568017)
Skelet Muscle. 2011 Nov 01;1:34. (PMID: 22040608)
J Clin Invest. 2010 Jan;120(1):11-9. (PMID: 20051632)
Nat Cell Biol. 2008 Jan;10(1):77-84. (PMID: 18066051)
Development. 2014 Jul;141(14):2780-90. (PMID: 25005473)
Curr Opin Cell Biol. 2014 Apr;27:18-24. (PMID: 24680426)
Cell Death Dis. 2013 Jun 27;4:e692. (PMID: 23807221)
J Biol Chem. 2002 Oct 11;277(41):38731-6. (PMID: 12140279)
PLoS One. 2014 Feb 28;9(2):e90398. (PMID: 24587351)
J Cell Physiol. 2011 Jan;226(1):29-36. (PMID: 20672327)
Int J Mol Sci. 2013 May 23;14(6):10761-90. (PMID: 23702846)
Toxicol Sci. 2012 Jul;128(1):147-57. (PMID: 22523228)
Pharmacol Res. 2014 Jan;79:34-74. (PMID: 24269963)
Nat Med. 2007 May;13(5):597-603. (PMID: 17468767)
Genes Dev. 2003 Jan 1;17(1):7-30. (PMID: 12514095)
Nat Rev Mol Cell Biol. 2006 Jul;7(7):505-16. (PMID: 16829981)
J Cell Sci. 2000 Dec;113 Pt 23:4211-20. (PMID: 11069766)
Skelet Muscle. 2011 Sep 08;1:29. (PMID: 21902831)
Aging Cell. 2007 Aug;6(4):515-23. (PMID: 17559502)
Cell Stem Cell. 2012 Sep 7;11(3):333-45. (PMID: 22863532)
FEBS J. 2013 Nov;280(21):5258-68. (PMID: 23992425)
J Cell Biol. 2004 Aug 2;166(3):347-57. (PMID: 15277541)
Development. 2012 Aug;139(16):2857-65. (PMID: 22764051)
J Cell Sci. 2011 May 1;124(Pt 9):1465-76. (PMID: 21486951)
Science. 2005 Nov 11;310(5750):996-9. (PMID: 16284174)
Nat Cell Biol. 2001 Nov;3(11):1009-13. (PMID: 11715022)
Mol Cell Biol. 2000 Jun;20(11):3951-64. (PMID: 10805738)
J Cell Biol. 1999 Feb 22;144(4):631-43. (PMID: 10037786)
Science. 2007 Aug 10;317(5839):807-10. (PMID: 17690295)
Cancer Cell. 2006 Oct;10(4):281-93. (PMID: 17045206)
Int J Biochem Cell Biol. 2007;39(6):1177-89. (PMID: 17433758)
Mol Ther. 2015 Jun;23(6):1003-1021. (PMID: 25762009)
J Biol Chem. 1998 Apr 24;273(17):10436-44. (PMID: 9553102)
Diabetes. 2008 Apr;57(4):967-79. (PMID: 18162507)
J Cell Mol Med. 2011 Sep;15(9):1927-40. (PMID: 21029370)
Biochem J. 2012 Jan 15;441(2):553-69. (PMID: 22187936)
J Biol Chem. 2002 May 10;277(19):16426-32. (PMID: 11877423)
Trends Biochem Sci. 2011 Sep;36(9):457-69. (PMID: 21764321)
Cell Mol Life Sci. 2013 Jun;70(12):2159-74. (PMID: 23344255)
Nat Rev Cancer. 2010 Nov;10(11):745-59. (PMID: 20966920)
Physiology (Bethesda). 2008 Jun;23:160-70. (PMID: 18556469)
Cell. 1997 Apr 4;89(1):127-38. (PMID: 9094721)
Gene Ther. 2011 Sep;18(9):857-66. (PMID: 21490680)
Genes Dev. 2006 Sep 1;20(17):2450-64. (PMID: 16951257)
J Biol Chem. 2012 Nov 2;287(45):38379-89. (PMID: 22992743)
Biochem J. 2010 Aug 1;429(3):403-17. (PMID: 20626350)
J Clin Invest. 2003 Sep;112(6):843-52. (PMID: 12975469)
Development. 2007 Mar;134(6):1171-80. (PMID: 17301086)
Nat Cell Biol. 2002 May;4(5):E131-6. (PMID: 11988758)
Mol Biol Cell. 2005 Aug;16(8):3632-41. (PMID: 15930130)
J Biol Chem. 2004 Mar 5;279(10):9634-41. (PMID: 14676207)
EMBO J. 2007 May 2;26(9):2240-50. (PMID: 17446863)
Trends Immunol. 2005 Oct;26(10):535-42. (PMID: 16109502)
EMBO J. 2007 Mar 7;26(5):1245-56. (PMID: 17304211)
J Proteomics. 2012 Dec 21;77:344-56. (PMID: 23000592)
J Biol Chem. 2008 Aug 22;283(34):23224-34. (PMID: 18552402)
Stem Cells. 2012 Sep;30(9):1971-84. (PMID: 22730231)
J Biol Chem. 2014 Aug 22;289(34):23417-27. (PMID: 25006242)
Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1736-44. (PMID: 18263706)
FEBS J. 2013 Sep;280(17):4177-86. (PMID: 23551987)
Proc Nutr Soc. 2004 May;63(2):279-86. (PMID: 15294044)
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12. (PMID: 23401516)
Cell. 2000 Oct 13;103(2):239-52. (PMID: 11057897)
Trends Cell Biol. 2006 Jan;16(1):36-44. (PMID: 16325404)
Nature. 2005 Feb 17;433(7027):760-4. (PMID: 15716955)
J Muscle Res Cell Motil. 2004;25(8):645-55. (PMID: 15750849)
Hum Mutat. 2013 Jul;34(7):986-96. (PMID: 23553787)
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3581-6. (PMID: 14993597)
Front Horm Res. 2014;42:175-85. (PMID: 24732935)
Nat Rev Mol Cell Biol. 2008 Oct;9(10):747-58. (PMID: 18813292)
Annu Rev Biochem. 2006;75:19-37. (PMID: 16756483)
Endocrinology. 2010 Mar;151(3):865-75. (PMID: 20130113)
Am J Physiol Cell Physiol. 2003 Mar;284(3):C658-66. (PMID: 12444016)

Keywords: Obestatin signaling; Skeletal muscle; Skeletal muscle regeneration

0 (ARRB1 protein, human)
0 (Arrestins)
0 (GPR39 protein, human)
0 (Ghrelin)
0 (Receptors, G-Protein-Coupled)
0 (beta-Arrestin 1)
0 (beta-Arrestins)
0 (obestatin, human)

Date Created: 20150728 Date Completed: 20160601 Latest Revision: 20240523

20240523

PMC11108386

10.1007/s00018-015-1994-z

26211463