Document Detail

Titin-cap associates with, and regulates secretion of, Myostatin.
MedLine Citation:
PMID:  12209887     Owner:  NLM     Status:  MEDLINE    
Myostatin, a secreted growth factor, is a key negative regulator of skeletal muscle growth. To identify modifiers of Myostatin function, we screened for Myostatin interacting proteins. Using a yeast two-hybrid screen, we identified Titin-cap (T-cap) protein as interacting with Myostatin. T-cap is a sarcomeric protein that binds to the N-terminal domain of Titin and is a substrate of the titin kinase. Mammalian two-hybrid studies, in vitro binding assays and protein truncations in the yeast two-hybrid system verified the specific interaction between processed mature Myostatin and full-length T-cap. Analysis of protein-protein interaction using surface plasmon resonance (Biacore, Uppsala, Sweden) kinetics revealed a high affinity between Myostatin and T-cap with a KD of 40 nM. When T-cap was stably overexpressed in C(2)C(12) myoblasts, the rate of cell proliferation was significantly increased. Western analyses showed that production and processing of Myostatin were not altered in cells overexpressing T-cap, but an increase in the retention of mature Myostatin indicated that T-cap may block Myostatin secretion. Bioassay for Myostatin confirmed that conditioned media from myoblasts overexpressing T-cap contained lower levels of Myostatin. Given that Myostatin negatively regulates myoblast proliferation, the increase in proliferation observed in myoblasts overexpressing T-cap could thus be due to reduced Myostatin secretion. These results suggest that T-cap, by interacting with Myostatin, controls Myostatin secretion in myogenic precursor cells without affecting the processing step of precursor Myostatin.
Gina Nicholas; Mark Thomas; Brett Langley; Wayne Somers; Ketan Patel; C Fred Kemp; Mridula Sharma; Ravi Kambadur
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  193     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-04     Completed Date:  2002-09-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  120-31     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Animal Genomics, AgResearch, East Street, Hamilton, New Zealand.
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MeSH Terms
Blotting, Western
CHO Cells
Cell Division / drug effects
Cell Line
Culture Media, Conditioned / metabolism,  pharmacology
Genes, Reporter
Muscle Proteins / chemistry,  genetics,  metabolism*,  pharmacology
Muscle, Skeletal / cytology,  drug effects,  metabolism*,  secretion
Protein Binding / physiology
Saccharomyces cerevisiae
Sequence Deletion
Surface Plasmon Resonance
Transforming Growth Factor beta / chemistry,  genetics,  metabolism*,  secretion*
Two-Hybrid System Techniques
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Mstn protein, mouse; 0/Muscle Proteins; 0/Myostatin; 0/Tcap protein, mouse; 0/Transforming Growth Factor beta

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