Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

2013
journal article
article
48
cris.lastimport.wos2024-04-10T02:55:06Z
dc.abstract.enCyclase-associated proteins are highly con- served proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium- regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physio- logical functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.pl
dc.affiliationWydział Chemii : Zakład Chemii Organicznejpl
dc.contributor.authorPeche, Vivek S.pl
dc.contributor.authorHolak, Tadeusz - 214380 pl
dc.contributor.authorBurgute, Bhagyashri D.pl
dc.contributor.authorKosmas, Kosmaspl
dc.contributor.authorKale, Sushant P.pl
dc.contributor.authorWunderlich, Thomas F.pl
dc.contributor.authorElhamine, Fatihapl
dc.contributor.authorStehle, Robertpl
dc.contributor.authorPfizer, Gabrielepl
dc.contributor.authorNohroudi, Klauspl
dc.contributor.authorAddicks, Klauspl
dc.contributor.authorStöckigt, Florianpl
dc.contributor.authorSchrickel, Jan W.pl
dc.contributor.authorGallinger, Juliapl
dc.contributor.authorSchleicher, Michaelpl
dc.contributor.authorNoegel, Angelika A.pl
dc.date.accessioned2015-06-18T07:19:43Z
dc.date.available2015-06-18T07:19:43Z
dc.date.issued2013pl
dc.description.additionalNa publikacji autor podpisany: Tad A. Holakpl
dc.description.number3pl
dc.description.physical527-543pl
dc.description.volume70pl
dc.identifier.doi10.1007/s00018-012-1142-ypl
dc.identifier.eissn1420-9071pl
dc.identifier.issn1420-682Xpl
dc.identifier.urihttp://ruj.uj.edu.pl/xmlui/handle/item/9755
dc.languageengpl
dc.language.containerengpl
dc.rights.licencebez licencji
dc.subtypeArticlepl
dc.titleAblation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathypl
dc.title.journalCellular and Molecular Life Sciencespl
dc.typeJournalArticlepl
dspace.entity.typePublication
cris.lastimport.wos
2024-04-10T02:55:06Z
dc.abstract.enpl
Cyclase-associated proteins are highly con- served proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium- regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physio- logical functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.
dc.affiliationpl
Wydział Chemii : Zakład Chemii Organicznej
dc.contributor.authorpl
Peche, Vivek S.
dc.contributor.authorpl
Holak, Tadeusz - 214380
dc.contributor.authorpl
Burgute, Bhagyashri D.
dc.contributor.authorpl
Kosmas, Kosmas
dc.contributor.authorpl
Kale, Sushant P.
dc.contributor.authorpl
Wunderlich, Thomas F.
dc.contributor.authorpl
Elhamine, Fatiha
dc.contributor.authorpl
Stehle, Robert
dc.contributor.authorpl
Pfizer, Gabriele
dc.contributor.authorpl
Nohroudi, Klaus
dc.contributor.authorpl
Addicks, Klaus
dc.contributor.authorpl
Stöckigt, Florian
dc.contributor.authorpl
Schrickel, Jan W.
dc.contributor.authorpl
Gallinger, Julia
dc.contributor.authorpl
Schleicher, Michael
dc.contributor.authorpl
Noegel, Angelika A.
dc.date.accessioned
2015-06-18T07:19:43Z
dc.date.available
2015-06-18T07:19:43Z
dc.date.issuedpl
2013
dc.description.additionalpl
Na publikacji autor podpisany: Tad A. Holak
dc.description.numberpl
3
dc.description.physicalpl
527-543
dc.description.volumepl
70
dc.identifier.doipl
10.1007/s00018-012-1142-y
dc.identifier.eissnpl
1420-9071
dc.identifier.issnpl
1420-682X
dc.identifier.uri
http://ruj.uj.edu.pl/xmlui/handle/item/9755
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights.licence
bez licencji
dc.subtypepl
Article
dc.titlepl
Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy
dc.title.journalpl
Cellular and Molecular Life Sciences
dc.typepl
JournalArticle
dspace.entity.type
Publication

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