Linked Life Data

18174465

Source:http://linkedlifedata.com/resource/pubmed/id/18174465

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-2-29
pubmed:abstractText
Integrins and proteins that associate with integrins are implicated in normal cardiac muscle function and development. Unc-112 is a cytoplasmic adaptor protein required for the proper establishment of integrin junctions in Caenorhabditis elegans muscle. A vertebrate homolog of unc-112, kindlin-2, is an integrin-binding protein that is expressed in cardiac muscle, but its function is unknown. We sought to understand the role of kindlin-2 in the development and function of the mouse and zebrafish heart. In the mouse, we found that kindlin-2 is highly expressed in the heart and is enriched at intercalated discs and costameres. Targeted disruption of the murine kindlin-2 gene resulted in embryonic lethality before cardiogenesis. To better assess the role of kindlin-2 in cardiac muscle development, we used morpholinos to knockdown the kindlin-2 homolog in zebrafish (z-kindlin-2), which resulted in severe abnormalities of heart development. Morphant hearts were hypoplastic and dysmorphic and exhibited significantly reduced ventricular contractility. Ultrastructural analysis of these hearts revealed disrupted intercalated disc formation and a failure in the attachment of myofibrils to membrane complexes. We conclude that kindlin-2 is an essential component of the intercalated disc, is necessary for cytoskeletal organization at sites of membrane attachment, and is required for vertebrate myocardial formation and function. These findings provide the first characterization of the in vivo functions of this novel and critical regulator of cardiogenesis.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-31
pubmed:meshHeading
pubmed-meshheading:18174465-Animals, pubmed-meshheading:18174465-Carrier Proteins, pubmed-meshheading:18174465-Embryonic Stem Cells, pubmed-meshheading:18174465-Gene Expression Regulation, Developmental, pubmed-meshheading:18174465-Heart, pubmed-meshheading:18174465-Heart Defects, Congenital, pubmed-meshheading:18174465-Mice, pubmed-meshheading:18174465-Mice, Inbred Strains, pubmed-meshheading:18174465-Mice, Transgenic, pubmed-meshheading:18174465-Muscle, Skeletal, pubmed-meshheading:18174465-Muscle Proteins, pubmed-meshheading:18174465-Mutagenesis, pubmed-meshheading:18174465-Myocardial Contraction, pubmed-meshheading:18174465-Myocardium, pubmed-meshheading:18174465-Nuclear Proteins, pubmed-meshheading:18174465-Phenotype, pubmed-meshheading:18174465-Phosphoprotein Phosphatases, pubmed-meshheading:18174465-Sarcomeres, pubmed-meshheading:18174465-Zebrafish
pubmed:year
2008
pubmed:articleTitle
Kindlin-2 is an essential component of intercalated discs and is required for vertebrate cardiac structure and function.
pubmed:affiliation
Division of Pediatric Neurology, L3215 Women's Hospital, Ann Arbor, MI 48109-0203, USA. jamedowl@umich.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural