Nebulin regulates the assembly and lengths of the thin filaments in striated muscle

Abigail S. McElhinny, Catherine Schwach, Melinda Valichnac, Sarah Mount-Patrick, Carol Gregorio

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

In many tissues, actin monomers polymerize into actin (thin) filaments of precise lengths. Although the exact mechanisms involved remain unresolved, it is proposed that "molecular rulers" dictate the lengths of the actin filaments. The giant nebulin molecule is a prime candidate for specifying thin filament lengths in striated muscle, but this idea has never been proven. To test this hypothesis, we used RNA interference technology in rat cardiac myocytes. Live cell imaging and triple staining revealed a dramatic elongation of the preexisting thin filaments from their pointed ends upon nebulin knockdown, demonstrating its role in length maintenance; the barbed ends were unaffected. When the thin filaments were depolymerized with latrunculin B, myocytes with decreased nebulin levels reassembled them to unrestricted lengths, demonstrating its importance in length specification. Finally, knockdown of nebulin in skeletal myotubes revealed its involvement in myofibrillogenesis. These data are consistent with nebulin functioning as a thin filament ruler and provide insight into mechanisms dictating macromolecular assembly.

Original languageEnglish (US)
Pages (from-to)947-957
Number of pages11
JournalJournal of Cell Biology
Volume170
Issue number6
DOIs
StatePublished - Sep 12 2005

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Striated Muscle
Actin Cytoskeleton
Muscle Development
Skeletal Muscle Fibers
RNA Interference
Cardiac Myocytes
Muscle Cells
Actins
Maintenance
nebulin
Staining and Labeling
Technology

ASJC Scopus subject areas

  • Cell Biology

Cite this

Nebulin regulates the assembly and lengths of the thin filaments in striated muscle. / McElhinny, Abigail S.; Schwach, Catherine; Valichnac, Melinda; Mount-Patrick, Sarah; Gregorio, Carol.

In: Journal of Cell Biology, Vol. 170, No. 6, 12.09.2005, p. 947-957.

Research output: Contribution to journalArticle

McElhinny, Abigail S. ; Schwach, Catherine ; Valichnac, Melinda ; Mount-Patrick, Sarah ; Gregorio, Carol. / Nebulin regulates the assembly and lengths of the thin filaments in striated muscle. In: Journal of Cell Biology. 2005 ; Vol. 170, No. 6. pp. 947-957.
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