Universität zu Köln

Zheng, Xiaoxu, Reho, John J., Wirth, Brunhilde ORCID: 0000-0003-4051-5191 and Fisher, Steven A. (2015). TRA2 beta controls Mypt1 exon 24 splicing in the developmental maturation of mouse mesenteric artery smooth muscle. Am. J. Physiol.-Cell Physiol., 308 (4). S. C289 - 8. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1563

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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 2 beta (Tra2 beta), 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 Tra2 beta within the first week of life but not in maturity reduced splicing of Mypt1 E24 in MAs. Inactivation of Tra2 beta 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. TRA2 beta is required for specification during this period of maturation, and its inactivation alters the contractile properties of mature arterial smooth muscle.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zheng, Xiaoxu UNSPECIFIED UNSPECIFIED UNSPECIFIED Reho, John J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Brunhilde UNSPECIFIED orcid.org/0000-0003-4051-5191 UNSPECIFIED Fisher, Steven A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-412424
DOI:	10.1152/ajpcell.00304.2014
Journal or Publication Title:	Am. J. Physiol.-Cell Physiol.
Volume:	308
Number:	4
Page Range:	S. C289 - 8
Date:	2015
Publisher:	AMER PHYSIOLOGICAL SOC
Place of Publication:	BETHESDA
ISSN:	1522-1563
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MYOSIN PHOSPHATASE ISOFORMS; DROSOPHILA-MELANOGASTER; DIFFERENTIATION; HYPERTENSION; SEX; INNERVATION; RELAXATION; EXPRESSION; DIVERSITY; PROTEIN Multiple languages Cell Biology; Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41242