Characterization of nebulette and nebulin and emerging concepts of their roles for vertebrate Z-discs

Stefania Millevoi, Karoly Trombitas, Bernhard Kolmerer, Sawa Kostin, Jutta Schaper, Katarina Pelin, Henk Granzier, Siegfried Labeit

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Nebulin is an 800 kDa large actin-binding protein specific to skeletal muscle and thought to act as a molecular template that regulates the length of thin filaments. Recently, a 100 kDa nebulin-like protein has been described in the avian cardiac muscle and referred to as nebulette. We have determined the full-length (8 kb) cDNA sequence of the human nebulette. Its open reading frame (3044 bp) encodes a 109 kDa protein that shares extensive similarity with the C-terminal region of human nebulin. The C-terminal regions of nebulin and nebulette are identical in domain organization and share a family of highly related C-terminal repeats, a serine-rich domain with potential phosphorylation sites, and an SH3 domain. Immunoelectron-microscopy suggests that the C-terminal 30 kDa of nebulin and nebulette filaments integrate into the Z-disc lattice, whereas their N termini appear to project into the I-band. Gene mapping studies assign the human nebulette gene to chromosome 10p12, whereas the nebulin gene has been previously assigned to 2q21. Evolutionary constraints appear to have maintained identical modular arrangements in these two independent genes. Comparison of nebulin and nebulette cDNAs demonstrates that a subgroup of repeats within the C-terminal regions is regulated tissue-specifically and stage-dependently during development of both molecules. This leads to a substantial diversity of nebulin and nebulette isoforms. Their further study is likely to provide insights into how they contribute to the molecular diversity of Z-discs from different muscle tissues and fiber types.

Original languageEnglish (US)
Pages (from-to)111-123
Number of pages13
JournalJournal of Molecular Biology
Volume282
Issue number1
DOIs
StatePublished - Sep 11 1998
Externally publishedYes

Keywords

  • Differential splicing
  • Muscle ultrastructure
  • Nebulin and nebulette
  • SH3 domain
  • Vertebrate Z-discs

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Millevoi, S., Trombitas, K., Kolmerer, B., Kostin, S., Schaper, J., Pelin, K., Granzier, H., & Labeit, S. (1998). Characterization of nebulette and nebulin and emerging concepts of their roles for vertebrate Z-discs. Journal of Molecular Biology, 282(1), 111-123. https://doi.org/10.1006/jmbi.1998.1999