| Smoothelin-like 1 protein regulates myosin phosphatase-targeting subunit 1 expression during sexual development and pregnancy. | |
| | |
MedLine Citation:
|
PMID: 20634291 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Pregnancy coordinately alters the contractile properties of both vascular and uterine smooth muscles reducing systemic blood pressure and maintaining uterine relaxation. The precise molecular mechanisms underlying these pregnancy-induced adaptations have yet to be fully defined but are likely to involve changes in the expression of proteins regulating myosin phosphorylation. Here we show that smoothelin like protein 1 (SMTNL1) is a key factor governing sexual development and pregnancy induced adaptations in smooth and striated muscle. A primary target gene of SMTNL1 in these muscles is myosin phosphatase-targeting subunit 1 (MYPT1). Deletion of SMTNL1 increases expression of MYPT1 30-40-fold in neonates and during development expression of both SMTNL1 and MYPT1 increases over 20-fold. Pregnancy also regulates SMTNL1 and MYPT1 expression, and deletion SMTNL1 greatly exaggerates expression of MYPT1 in vascular smooth muscle, producing a profound reduction in force development in response to phenylephrine as well as sensitizing the muscle to acetylcholine. We also show that MYPT1 is expressed in Type2a muscle fibers in mice and humans and its expression is regulated during pregnancy, suggesting unrecognized roles in mediating skeletal muscle plasticity in both species. Our findings define a new conserved pathway in which sexual development and pregnancy mediate smooth and striated muscle adaptations through SMTNL1 and MYPT1. |
| | |
Authors:
|
Beata Lontay; Khaldon Bodoor; Douglas H Weitzel; David Loiselle; Christopher Fortner; Szabolcs Lengyel; Donghai Zheng; James Devente; Robert Hickner; Timothy A J Haystead |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-15 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Sep |
Date Detail:
|
Created Date: 2010-09-13 Completed Date: 2010-09-28 Revised Date: 2012-04-26 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 29357-66 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Animals Blotting, Western Cell Nucleus / metabolism Female Gene Expression Regulation, Developmental Humans Immunohistochemistry Male Mice Mice, Mutant Strains Microscopy, Confocal Muscle Proteins / genetics, metabolism* Muscle, Smooth / metabolism* Muscle, Striated / metabolism* Myosin-Light-Chain Kinase / genetics, metabolism* Phosphoproteins / genetics, metabolism* Phosphorylation Pregnancy Protein Binding / genetics, physiology Protein Transport / genetics, physiology Reverse Transcriptase Polymerase Chain Reaction Uterus / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
R01DK065954-05/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/CHASM protein, mouse; 0/Muscle Proteins; 0/Phosphoproteins; EC 2.7.11.18/Myosin-Light-Chain Kinase; EC 3.1.3.53/MYPT1 protein, mouse |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscula...
Next Document: Tissue-nonspecific alkaline phosphatase promotes the neurotoxicity effect of extracellular tau.