Novex-3, the tiny titin of muscle

Dalma Kellermayer, John E. Smith, Henk Granzier

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

The giant multi-functional striated muscle protein titin is the third most abundant muscle protein after myosin and actin. Titin plays a pivotal role in myocardial passive stiffness, structural integrity and stress-initiated signaling pathways. The complete sequence of the human titin gene contains three isoform-specific mutually exclusive exons [termed novel exons (novex)] coding for the I-band sequence, named novex-1 (exon 45), novex-2 (exon 46) and novex-3 (exon 48). Transcripts containing either the novex-1 or novex-2 exons code for the novex-1 and novex-2 titin isoforms. The novex-3 transcript contains a stop codon and polyA tail signal, resulting in an unusually small (∼700 kDa) isoform, referred to as novex-3 titin. This ‘tiny titin’ isoform extends from the Z-disc (N-terminus) to novex-3 (C-terminus) and is expressed in all striated muscles. Biochemical analysis of novex-3 titin in cardiomyocytes shows that obscurin, a vertebrate muscle protein, binds to novex-3 titin. The novex-3/obscurin complex localizes to the Z-disc region and may regulate calcium, and SH3- and GTPase-associated myofibrillar signaling pathways. Therefore, novex-3 titin could be involved in stress-initiated sarcomeric restructuring.

Original languageEnglish (US)
Pages (from-to)201-206
Number of pages6
JournalBiophysical Reviews
Volume9
Issue number3
DOIs
StatePublished - Jun 1 2017

Keywords

  • Novex-3 titin
  • Obscurin
  • TTN sequence
  • Titin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology

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