Nebulin

Nebulin is an is_associated_with::actin-binding protein which is localized to the thin filament of the is_associated_with::sarcomeres in is_associated_with::skeletal muscle. It is a very large protein (600-900 kDa) and binds as many as 200 actin monomers. Because its length is proportional to thin filament length, it is believed that nebulin acts as a thin filament "ruler" and regulates thin filament length during is_associated_with::sarcomere assembly. Other functions of nebulin, such as a role in is_associated_with::cell signaling, remain uncertain.

Nebulin has also been shown to regulate actin-myosin interactions by inhibiting is_associated_with::ATPase activity in a is_associated_with::calcium-is_associated_with::calmodulin sensitive manner.

is_associated_with::Mutations in nebulin cause some cases of the is_associated_with::autosomal recessive disorder is_associated_with::nemaline myopathy.

A smaller member of the nebulin protein family termed is_associated_with::nebulette, is expressed in is_associated_with::cardiac muscle.

Structure
The structure of the is_associated_with::SH3 domain of nebulin was determined by NMR. The SH3 domain from nebulin is composed of 60 amino acid residues, of which 30 percent is in the is_associated_with::beta sheet secondary structure (7 strands; 18 residues).

Knockout phenotype
As of 2007, two is_associated_with::knockout mouse models for nebulin have been developed to better understand its in vivo function. Bang and colleagues demonstrated that nebulin-knockout mice die postnatally, have reduced thin filament length, and impaired contractile function. Postnatal is_associated_with::sarcomere disorganization and degeneration occurred rapidly in these mice, indicating the nebulin is essential for maintaining the structural integrity of is_associated_with::myofibrils. Witt and colleagues had similar results in their mice, which also died postnatally with reduced thin filament length and contractile function. These nebulin-knockout mice are being investigated as is_associated_with::animal models of is_associated_with::nemaline myopathy.