Novex-3, the tiny titin of muscle

Biophysics Reviews
Dalma KellermayerHenk Granzier

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.

References

Jan 12, 2001·Journal of Molecular Biology·A D LiversageJ Trinick
Sep 11, 2002·Circulation·Ciprian NeagoeWolfgang A Linke
Nov 22, 2002·The Journal of Biological Chemistry·Aikaterini Kontrogianni-Konstantopoulos, Robert J Bloch
Feb 21, 2004·Circulation Research·Henk L Granzier, Siegfried Labeit
Feb 28, 2004·Circulation Research·Christiane A OpitzWolfgang A Linke
Aug 24, 2004·The Journal of Biological Chemistry·Larissa Tskhovrebova, John Trinick
Mar 16, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Masahiko Hoshijima
Apr 25, 2006·Gene Expression Patterns : GEP·Daniel D BrownFrank L Conlon
May 9, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Martina KrügerWolfgang A Linke
Oct 14, 2006·Journal of Cell Science·Hanny MusaMichelle Peckham
May 25, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Henk GranzierSiegfried Labeit
Jan 25, 2011·The Journal of Biological Chemistry·Martina Krüger, Wolfgang A Linke
Feb 18, 2012·The New England Journal of Medicine·Daniel S HermanChristine E Seidman
Apr 3, 2012·Nature Medicine·Wei GuoMichael Gotthardt
Feb 27, 2013·Circulation·Martin M LeWinter, Henk L Granzier
Feb 12, 2014·PloS One·Maegen A AckermannAikaterini Kontrogianni-Konstantopoulos
Jul 2, 2014·Human Mutation·Claire ChauveauAna Ferreiro
Nov 28, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Florian HinzeMichael Gotthardt

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Citations

Jan 15, 2018·Biophysics Reviews·Cristobal G Dos Remedios
Mar 29, 2019·Pflügers Archiv : European journal of physiology·Dalma KellermayerHenk Granzier
Aug 19, 2018·Scientific Reports·Ken HashimotoSatoshi Mohri
Sep 11, 2020·Basic Research in Cardiology·Alyssa GroganAikaterini Kontrogianni-Konstantopoulos
Feb 20, 2020·Seminars in Cell & Developmental Biology·Elena NikonovaMaria L Spletter

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Methods Mentioned

BETA
PCR
two-hybrid
transfection
pull-down
GTPase

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