title: Nebulin regulates actin filament lengths by a stabilization mechanism.
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.
authors.affiliation: Department of Cell Biology and Anatomy and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Pappas
authors.forename: Paul A
authors.initials: PA
authors.lastname: Krieg
authors.forename: Carol C
authors.initials: CC
authors.lastname: Gregorio
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002645:Chickens; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D053778:Thiazolidines / Q000494:pharmacology; D014162:Transfection; D051348:Tropomodulin / Q000378:metabolism
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D009124:Muscle Proteins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D053778:Thiazolidines; D051348:Tropomodulin; C035620:nebulin; C037067:latrunculin A