NDLI: Genetic Analysis of the Role of Proteolysis in the Activation of Latent Myostatin

Content Provider	PubMed Central
Author	Lee, Se-jin
Editor	Volff, Jean-nicolas
Copyright Year	2008
Abstract	Myostatin is a secreted protein that normally acts to limit skeletal muscle growth. As a result, there is considerable interest in developing agents capable of blocking myostatin activity, as such agents could have widespread applications for the treatment of muscle degenerative and wasting conditions. Myostatin normally exists in an inactive state in which the mature C-terminal portion of the molecule is bound non-covalently to its N-terminal propeptide. We previously showed that this latent complex can be activated in vitro by cleavage of the propeptide with members of the bone morphogenetic protein-1/tolloid (BMP-1/TLD) family of metalloproteases. Here, I show that mice engineered to carry a germline point mutation rendering the propeptide protease-resistant exhibit increases in muscle mass approaching those seen in mice completely lacking myostatin. Mice homozygous for the point mutation have increased muscling even though their circulating levels of myostatin protein are dramatically increased, consistent with an inability of myostatin to be activated from its latent state. Furthermore, I show that a loss-of-function mutation in Tll2, which encodes one member of this protease family, has a small, but significant, effect on muscle mass, implying that its function is likely redundant with those of other family members. These findings provide genetic support for the hypothesis that proteolytic cleavage of the propeptide by BMP-1/TLD proteases plays a critical role in the activation of latent myostatin in vivo and suggest that targeting the activities of these proteases may be an effective therapeutic strategy for enhancing muscle growth in clinical settings of muscle loss and degeneration.
Related Links	http://dx.doi.org/10.1371/journal.pone.0001628
Starting Page	1628
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	2
Volume Number	3
Language	English
Publisher	Public Library of Science
Publisher Date	2008-02-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Glucocorticoids Enhance Muscle Proteolysis through a Myostatin-Dependent Pathway at the Early Stage

Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise

Activation of Latent HIV Using Drug-Loaded Nanoparticles

MicroRNA-Mediated Myostatin Silencing in Caprine Fetal Fibroblasts

Postnatal PPARδ Activation and Myostatin Inhibition Exert Distinct yet Complimentary Effects on the Metabolic Profile of Obese Insulin-Resistant Mice

Transcriptomic Analysis of Human Polarized Macrophages: More than One Role of Alternative Activation?

Cytotoxic Aggregation and Amyloid Formation by the Myostatin Precursor Protein

The Role of Potassium Channel Activation in Celecoxib-Induced Analgesic Action

Analysis of the Putative Role of CR1 in Alzheimer’s Disease: Genetic Association, Expression and Function

Genetic Analysis of the Role of Proteolysis in the Activation of Latent Myostatin

Similar Documents

Glucocorticoids Enhance Muscle Proteolysis through a Myostatin-Dependent Pathway at the Early Stage

Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise

Activation of Latent HIV Using Drug-Loaded Nanoparticles

MicroRNA-Mediated Myostatin Silencing in Caprine Fetal Fibroblasts

Postnatal PPARδ Activation and Myostatin Inhibition Exert Distinct yet Complimentary Effects on the Metabolic Profile of Obese Insulin-Resistant Mice

Transcriptomic Analysis of Human Polarized Macrophages: More than One Role of Alternative Activation?

Cytotoxic Aggregation and Amyloid Formation by the Myostatin Precursor Protein

The Role of Potassium Channel Activation in Celecoxib-Induced Analgesic Action

Analysis of the Putative Role of CR1 in Alzheimer’s Disease: Genetic Association, Expression and Function

Genetic Analysis of the Role of Proteolysis in the Activation of Latent Myostatin