Nebulin regulates actin filament lengths by a stabilization mechanism

Efficient muscle contraction requires regulation of actin filament lengths. In one highly cited model, the giant protein nebulin has been proposed to function as a molecular ruler specifying filament lengths. We directly challenged this hypothesis by constructing a unique, small version of nebulin (...

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Bibliographic Details
Published in:The Journal of cell biology 2010-05, Vol.189 (5), p.859-870
Main Authors: Pappas, Christopher T, Krieg, Paul A, Gregorio, Carol C
Format: Article
Language:English
Subjects:
Actin Cytoskeleton - drug effects
Actin Cytoskeleton - metabolism
Actins
Actins - metabolism
Animals
Antibodies
Biochemistry
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
Cells
Cellular biology
Chickens
Depolymerization
Humans
Hypotheses
Microfilaments
Muscle fibers
Muscle Fibers, Skeletal - drug effects
Muscle Fibers, Skeletal - metabolism
Muscle Proteins - genetics
Muscle Proteins - metabolism
Peptide Fragments - genetics
Peptide Fragments - metabolism
Physiological regulation
Proteins
RNA, Small Interfering - genetics
Sarcomeres
Skeletal muscle
Small interfering RNA
Thiazolidines - pharmacology
Transfection
Tropomodulin - metabolism
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Summary:Efficient muscle contraction requires regulation of actin filament lengths. In one highly cited model, the giant protein nebulin has been proposed to function as a molecular ruler specifying filament lengths. We directly challenged this hypothesis by constructing a unique, small version of nebulin (mini-nebulin). When endogenous nebulin was replaced with mini-nebulin in skeletal myocytes, thin filaments extended beyond the end of mini-nebulin, an observation which is inconsistent with a strict ruler function. However, under conditions that promote actin filament depolymerization, filaments associated with mini-nebulin were remarkably maintained at lengths either matching or longer than mini-nebulin. This indicates that mini-nebulin is able to stabilize portions of the filament it has no contact with. Knockdown of nebulin also resulted in more dynamic populations of thin filament components, whereas expression of mini-nebulin decreased the dynamics at both filament ends (i.e., recovered loss of endogenous nebulin). Thus, nebulin regulates thin filament architecture by a mechanism that includes stabilizing the filaments and preventing actin depolymerization.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201001043