NEBULIN

'Nebulin' is an actin-binding protein which is localized to the I-band the sarcomeres in 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 sarcomere assembly.^[1] Other functions of nebulin, such as a role in cell signaling, remain uncertain.
The interaction of nebulin with actin is calcium-calmodulin sensitive.^[2]
Mutations in nebulin cause some cases of the autosomal recessive disorder nemaline myopathy.^[3]
A second smaller isoform of nebulin, termed nebulette, is expressed in cardiac muscle.

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Knockout phenotype

References

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Knockout phenotype

As of 2007, two knockout mouse models for nebulin have been developed to better understand its ''in vivo'' function. Bang and colleagues^[4] demonstrated that nebulin-knockout mice die postnatally, have reduced thin filament length, and impaired contractile function. Postnatal sarcomere disorganization and degeneration occurred rapidly in these mice, indicating the nebulin is essential for maintaining the structural integrity of myofibrils. Witt and colleagues^[5] 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 animal models of nemaline myopathy.

References

1. Nebulin: the nebulous, multifunctional giant of striated muscle, McElhinny et al, , , Trends Cardiovasc Med, 2003
2. Calmodulin-sensitive interaction of human nebulin fragments with actin and myosin, Root & Wang, , , Biochemistry, 1994
3. Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy, Pelin et al, , , Proc Natl Acad Sci USA, 1999
4. Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle, Bang et al, , , J Cell Biol, 2006
5. Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo, Witt et al, , , EMBO J, 2006

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