Nebulin is an

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

-binding protein which is localized to the thin filament of the

sarcomeres A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called musc ...

in skeletal muscle. Nebulin in humans is coded for by the

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

''NEB''. 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 Myofilaments are the three protein filaments of myofibrils in muscle cells. The main proteins involved are myosin, actin, and titin. Myosin and actin are the ''contractile proteins'' and titin is an elastic protein. The myofilaments act together ...

length, it is believed that nebulin acts as a thin filament "ruler" and regulates thin filament length during

sarcomere A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called mus ...

assembly and acts as the coats the actin filament. Other functions of nebulin, such as a role in

cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

, remain uncertain. Nebulin has also been shown to regulate actin-myosin interactions by inhibiting ATPase activity in a

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

- calmodulin sensitive manner. Mutations in nebulin cause some cases of the autosomal recessive disorder

nemaline myopathy Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ...

. A smaller member of the nebulin protein family, termed

nebulette Nebulette is a cardiac-specific isoform belonging to the nebulin family of proteins. It is encoded by the ''NEBL'' gene. This family is composed of 5 members: nebulette, nebulin, N-RAP, LASP-1 and LASP-2. Nebulette localizes to Z-discs of cardi ...

, is expressed in

cardiac muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

Structure

The structure of the

SH3 domain The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phos ...

of nebulin was determined by protein nuclear magnetic resonance spectroscopy.; The SH3 domain from nebulin is composed of 60 amino acid residues, of which 30 percent is in the beta sheet secondary structure (7 strands; 18 residues).

Knockout phenotype

As of 2007, two

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importa ...

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

disorganization and degeneration occurred rapidly in these mice, indicating the nebulin is essential for maintaining the structural integrity of

myofibril A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as muscle fibers, and these cells contain many chains of myofibrils. Each myo ...

s. 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

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

s of

References

External links

*
GeneReviews/NCBI/NIH/UW entry on Nemaline Myopathy

PDBe-KB
provides an overview of all the structure information available in the PDB for Human Nebulin {{Muscle tissue Proteins

Structure

Knockout phenotype

References

Further reading

External links