Peptidyl‐prolyl cis–trans isomerase NIMA interacting 1 regulates skeletal muscle fusion through structural modification of Smad3 in the linker region. Issue 12 (21st August 2018)

• Record Type: Journal Article
• Authors: Islam, Rabia; Yoon, Heein; Shin, Hye‐Rim; Bae, Han‐Sol; Kim, Bong‐Soo; Yoon, Won‐Joon; Woo, Kyung‐Mi; Baek, Jeong‐Hwa; Lee, Yun‐Sil; Ryoo, Hyun‐Mo
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 12(2018:Dec.)
• Page Start: 9390
• Page End: 9403
• Publication Date: 2018-08-21
• Subjects: cell fusion -- ERK -- myoblast -- peptidyl‐prolyl cis–trans isomerase NIMA interacting 1 -- Smad3 -- TGF superfamily; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26774
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Myoblast fusion is critical for muscle growth, regeneration, and repair. We previously reported that the enzyme peptidyl‐prolyl cis–trans isomerase NIMA interacting 1 (Pin1) is involved in osteoclast fusion. The objective of this study was to investigate the possibility that Pin1 also inhibits myoblast fusion. Here, we show the increased number of nuclei in the Pin1 +/− mice muscle fiber compared to that in wild‐type mice. Moreover, we show that low dose of the Pin1 inhibitor dipentamethylene thiuram monosulfide treatment caused enhanced fusion in C2C12 cells. The R‐Smads are well‐known mediators of muscle hypertrophy and hyperplasia as well as being substrates of Pin1. We found that Pin1 is crucial for maintaining the stability of Smad3 (homologues of the Drosophila protein, mothers against decapentaplegic (Mad) and the Caenorhabditis elegans protein Sma). Our results show that serine 204 within Smad3 is the key Pin1‐binding site during inhibition of myoblast fusion and that both the transforming growth factor‐β receptor and extracellular signal‐regulated kinase (ERK)‐mediated phosphorylation are required for the interaction of Pin1 with Smad3. These findings suggest that a precise level of Pin1 activity is essential for regulating myoblast fusion during myogenesis and muscle regeneration. Abstract : Myoblast fusion is pivotal for muscle development. We found that postphosphorylation isomerization of Smad3 by Pin1 is a crucial mechanism that governs myoblast fusion and maintains muscle mass.