Universität zu Köln

Puetz, Sandra, Barthel, Lisa Sophie, Frohn, Marina, Metzler, Doris, Barham, Mohammed, Pryymachuk, Galyna, Trunschke, Oliver, Lubomirov, Lubomir T., Hescheler, Jurgen, Chalovich, Joseph M., Neiss, Wolfram F., Koch, Manuel ORCID: 0000-0002-2962-7814, Schroeter, Mechthild M. and Pfitzer, Gabriele (2021). Caldesmon ablation in mice causes umbilical herniation and alters contractility of fetal urinary bladder smooth muscle. J. Gen. Physiol., 153 (7). NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-7748

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Abstract

The actin-, myosin-, and calmodulin-binding protein caldesmon (CaD) is expressed in two splice isoforms: h-CaD, which is an integral part of the actomyosin domain of smooth muscle cells, and l-CaD, which is widely expressed and is involved in many cellular functions. Despite extensive research for many years, CaD's in vivo function has remained elusive. To explore the role of CaD in smooth muscle contraction in vivo, we generated a mutant allele that ablates both isoforms. Heterozygous animals were viable and had a normal life span, but homozygous mutants died perinatally, likely because of a persistent umbilical hernia. The herniation was associated with hypoplastic and dysmorphic abdominal wall muscles. We assessed mechanical parameters in isometrically mounted longitudinal strips of E18.5 urinary bladders and in ring preparations from abdominal aorta using wire myography. Ca2+ sensitivity was higher and relaxation rate was slower in Calc1(-/-) compared with Cold1(+/+) skinned bladder strips. However, we observed no change in the content and phosphorylation of regulatory proteins of the contractile apparatus and myosin isoforms known to affect these contractile parameters. Intact fibers showed no difference in actin and myosin content, regardless of genotype, although KO-induced force tended to be lower in homozygous and higher in heterozygous mutants than in WTs. Conversely, in skinned fibers, myosin content and maximal force were significantly lower in Cold1(-/-) than in WTs. In KO abdominal aortas, resting and U46619 elicited force were lower than in WTs. Our results are consistent with the notion that CaD impacts smooth muscle function dually by (1) acting as a molecular brake on contraction and (2) maintaining the structural integrity of the contractile machinery. Most importantly, CaD is essential for resolution of the physiological umbilical hernia and ventral body wall closure.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Puetz, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Barthel, Lisa Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Frohn, Marina UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzler, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Barham, Mohammed UNSPECIFIED UNSPECIFIED UNSPECIFIED Pryymachuk, Galyna UNSPECIFIED UNSPECIFIED UNSPECIFIED Trunschke, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Lubomirov, Lubomir T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Chalovich, Joseph M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neiss, Wolfram F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Schroeter, Mechthild M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfitzer, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-577859
DOI:	10.1085/jgp.202012776
Journal or Publication Title:	J. Gen. Physiol.
Volume:	153
Number:	7
Date:	2021
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-7748
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VENTRAL BODY-WALL; HEAVY-MEROMYOSIN; ATPASE ACTIVITY; MYOSIN PHOSPHORYLATION; BINDING-PROTEIN; LIGHT-CHAIN; CA2+-INDEPENDENT CONTRACTION; MG-2+-ATPASE ACTIVITY; ACTIN CYTOSKELETON; FUNCTIONAL DOMAIN Multiple languages Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57785