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PMID:20498015

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Citation

Pappas, CT, Krieg, PA and Gregorio, CC (2010) Nebulin regulates actin filament lengths by a stabilization mechanism. J. Cell Biol. 189:859-70

Abstract

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.

Links

PubMed PMC2878950 Online version:10.1083/jcb.201001043

Keywords

Actin Cytoskeleton/drug effects; Actin Cytoskeleton/metabolism; Actins/metabolism; Animals; Bicyclo Compounds, Heterocyclic/pharmacology; Chickens; Humans; Muscle Fibers, Skeletal/drug effects; Muscle Fibers, Skeletal/metabolism; Muscle Proteins/genetics; Muscle Proteins/metabolism; Peptide Fragments/genetics; Peptide Fragments/metabolism; RNA, Small Interfering/genetics; Thiazolidines/pharmacology; Transfection; Tropomodulin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CHICK:Q90684

involved_in

GO:0030835: negative regulation of actin filament depolymerization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000737)
  • occurs_in:(UBERON:0001495)

Seeded From UniProt

complete

CHICK:Q9DEH4

GO:0005198: structural molecule activity

ECO:0000315:

F

Figure 3

complete

CHICK:Q9DEH4

GO:0030835: negative regulation of actin filament depolymerization

ECO:0000315:

P

Figure 1

complete


See also

References

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