Faculty Collaboration Database

TRA2β controls Mypt1 exon 24 splicing in the developmental maturation of mouse mesenteric artery smooth muscle. Am J Physiol Cell Physiol 2015 Feb 15;308(4):C289-96

Date

11/28/2014

Pubmed ID

25428883

Pubmed Central ID

PMC4329427

DOI

10.1152/ajpcell.00304.2014

Scopus ID

2-s2.0-85047700459 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Diversity of smooth muscle within the vascular system is generated by alternative splicing of exons, yet there is limited understanding of its timing or control mechanisms. We examined splicing of myosin phosphatase regulatory subunit (Mypt1) exon 24 (E24) in relation to smooth muscle myosin heavy chain (Smmhc) and smoothelin (Smtn) alternative exons (Smmhc E6 and Smtn E20) during maturation of mouse mesenteric artery (MA) smooth muscle. The role of transformer 2β (Tra2β), a master regulator of splicing in flies, in maturation of arterial smooth muscle was tested through gene inactivation. Splicing of alternative exons in bladder smooth muscle was examined for comparative purposes. MA smooth muscle maturation began after postnatal week 2 and was complete at maturity, as indicated by switching to Mypt1 E24+ and Smtn E20- splice variants and 11-fold induction of Smmhc. Similar changes in bladder were complete by postnatal day 3. Splicing of Smmhc E6 was temporally dissociated from Mypt1 E24 and Smtn E20 and discordant between arteries and bladder. Tamoxifen-induced smooth muscle-specific inactivation of Tra2β within the first week of life but not in maturity reduced splicing of Mypt1 E24 in MAs. Inactivation of Tra2β causing a switch to the isoform of MYPT1 containing the COOH-terminal leucine zipper motif (E24-) increased arterial sensitivity to cGMP-mediated relaxation. In conclusion, maturation of mouse MA smooth muscle begins postnatally and continues until sexual maturity. TRA2β is required for specification during this period of maturation, and its inactivation alters the contractile properties of mature arterial smooth muscle.

Author List

Zheng X, Reho JJ, Wirth B, Fisher SA

Author

John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age Factors
Alternative Splicing
Animals
Cell Differentiation
Cyclic GMP
Cytoskeletal Proteins
Dose-Response Relationship, Drug
Exons
Female
Gene Expression Regulation, Developmental
Genotype
In Vitro Techniques
Male
Mesenteric Arteries
Mice, Inbred C57BL
Mice, Knockout
Muscle Proteins
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Myosin Heavy Chains
Myosin-Light-Chain Kinase
Myosin-Light-Chain Phosphatase
Nuclear Proteins
Phenotype
RNA-Binding Proteins
Serine-Arginine Splicing Factors
Smooth Muscle Myosins
Vasodilation
Vasodilator Agents