Cardiac titin: A multifunctional giant

Martin M. Lewinter, Hendrikus "Henk" Granzier

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Titin is responsible for the passive and restoring force of the cardiac sarcomere and makes a major contribution to the diastolic wall stress of the LV, the level of which can be tuned through differential splicing and phosphorylation. PKA and PKG phosphorylation lower stress, and PKC increases it. Changes in titin phosphorylation and titin splicing occur in cardiac disease, in addition to mutations in the titin gene. A host of titin-binding proteins have been discovered that implicate titin as a key player in the organization and development of the sarcomere, in protein turnover, and in sensing mechanical stress. Several stress-sensing signalosomes along the molecule have been discovered, of which only the FHL-based signalosome binds to a spring element (N2B). This N2B-FHL signalosome is ideally situated to sense sarcomere strain and link diastolic dysfunction to hypertrophy signaling.

Original languageEnglish (US)
Pages (from-to)2137-2145
Number of pages9
JournalCirculation
Volume121
Issue number19
DOIs
StatePublished - May 18 2010

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Connectin
Sarcomeres
Phosphorylation
Mechanical Stress
Hypertrophy
Heart Diseases
Carrier Proteins
Mutation
Genes

Keywords

  • Cardiomyopathy
  • Diastole
  • Hypertrophy
  • Myocardium
  • Titin

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Cardiac titin : A multifunctional giant. / Lewinter, Martin M.; Granzier, Hendrikus "Henk".

In: Circulation, Vol. 121, No. 19, 18.05.2010, p. 2137-2145.

Research output: Contribution to journalArticle

Lewinter, Martin M. ; Granzier, Hendrikus "Henk". / Cardiac titin : A multifunctional giant. In: Circulation. 2010 ; Vol. 121, No. 19. pp. 2137-2145.
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