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

Autor: Sarah Mount-Patrick, Abigail S. McElhinny, Carol C. Gregorio, Catherine Schwach, Melinda Valichnac
Rok vydání: 2005
Předmět:
Blotting
Western
Muscle Proteins
macromolecular substances
Acetates
Muscle Development
Transfection
Article
Myoblasts
03 medical and health sciences
Nebulin
0302 clinical medicine
Live cell imaging
Animals
Myocyte
Myocytes
Cardiac
RNA
Small Interfering
Fluorescent Antibody Technique
Indirect
Muscle
Skeletal
Research Articles
Cells
Cultured
Actin
Fluorescent Dyes
030304 developmental biology
0303 health sciences
Gene knockdown
Dose-Response Relationship
Drug
biology
Reverse Transcriptase Polymerase Chain Reaction
Myogenesis
Antibodies
Monoclonal
Gene Expression Regulation
Developmental
RNA
Cell Biology
Bridged Bicyclo Compounds
Heterocyclic
Actins
Rats
Macromolecular assembly
Thiazoles
Microscopy
Fluorescence
Xanthenes
Biochemistry
Chromones
biology.protein
Biophysics
Thiazolidines
030217 neurology & neurosurgery
Zdroj: The Journal of Cell Biology
ISSN: 1540-8140
0021-9525
DOI: 10.1083/jcb.200502158
Popis: 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.
Databáze: OpenAIRE
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