The NH2 terminus of titin spans the Z-disc: Its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity

Carol C. Gregorio, Karoly Trombitás, Thomas Centner, Bernhard Kolmerer, Gunter Stier, Kathleen Kunke, Koichi Suzuki, Franz Obermayr, Bernhard Herrmann, Henk Granzier, Hiroyuki Sorimachi, Siegfried Labeit

Research output: Contribution to journalArticle

227 Scopus citations

Abstract

Titin is a giant elastic protein in vertebrate striated muscles with an unprecedented molecular mass of 3-4 megadaltons. Single molecules of titin extend from the Z-line to the M-line. Here, we define the molecular layout of titin within the Z-line; the most NH2-terminal 30 kD of titin is located at the periphery of the Z-line at the border of the adjacent sarcomere, whereas the subsequent 60 kD of titin spans the entire width of the Z-line. In vitro binding studies reveal that mammalian titins have at least four potential binding sites for α-actinin within their Z-line spanning region. Titin filaments may specify Z-line width and internal structure by varying the length of their NH2-terminal overlap and number of α-actinin binding sites that serve to cross-link the titin and thin filaments. Furthermore, we demonstrate that the NH2-terminal titin Ig repeats Z1 and Z2 in the periphery of the Z-line bind to a novel 19-kD protein, referred to as titin- cap. Using dominant-negative approaches in cardiac myocytes, both the titin Z1-Z2 domains and titin-cap are shown to be required for the structural integrity of sarcomeres, suggesting that their interaction is critical in titin filament-regulated sarcomeric assembly.

Original languageEnglish (US)
Pages (from-to)1013-1027
Number of pages15
JournalJournal of Cell Biology
Volume143
Issue number4
DOIs
StatePublished - Nov 16 1998

Keywords

  • Sarcomere
  • Titin
  • Titin-cap (T-cap)
  • Z-disc
  • α-actinin

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'The NH<sub>2</sub> terminus of titin spans the Z-disc: Its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity'. Together they form a unique fingerprint.

  • Cite this

    Gregorio, C. C., Trombitás, K., Centner, T., Kolmerer, B., Stier, G., Kunke, K., Suzuki, K., Obermayr, F., Herrmann, B., Granzier, H., Sorimachi, H., & Labeit, S. (1998). The NH2 terminus of titin spans the Z-disc: Its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. Journal of Cell Biology, 143(4), 1013-1027. https://doi.org/10.1083/jcb.143.4.1013