Linked Life Data

16533505

Source:http://linkedlifedata.com/resource/pubmed/id/16533505

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-4-24
pubmed:abstractText
A central question in muscle biology is how costameres are formed and become aligned with underlying myofibrils in mature tissues. Costameres are composed of focal adhesion proteins, including vinculin and paxillin, and anchor myofibril Z-bands to the sarcolemma. In the present study, we investigated the process of costamere formation ("costamerogenesis") in differentiating primary mouse myoblasts. Using vinculin and paxillin as costameric markers, we found that two additional focal adhesion components, alpha5beta1 integrin and focal adhesion kinase (FAK), are associated with costameres. We have characterized costamerogenesis as occurring in three distinct stages based on the organizational pattern of these costameric proteins. We show that both costamerogenesis and myofibrillogenesis are initiated at sites of membrane contacts with the extracellular matrix and that their maturation is tightly coupled. To test the importance of FAK signaling in these processes, we analyzed cells expressing a dominant negative form of FAK (dnFAK). When cells expressing dnFAK were induced to differentiate, both costamerogenesis and myofibrillogenesis were disrupted although the expression of constituent proteins was not inhibited. Likewise, inhibiting FAK activity by reducing FAK levels using an siRNA approach also resulted in an inhibition of costamerogenesis and myofibrillogenesis. The relationship between costamere and myofibril formation was tested further by treating myotube cultures with potassium or tetrodotoxin to block contraction and disrupt myofibril organization. This also resulted in inhibition of costamere maturation. We present a model of costamerogenesis whereby signaling through FAK is essential for both normal costamerogenesis and normal myofibrillogenesis which are tightly coupled during skeletal myogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0012-1606
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Focal adhesion kinase is essential for costamerogenesis in cultured skeletal muscle cells.
pubmed:affiliation
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural