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 ...

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

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

. Nebulin in humans is coded for by the

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

''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 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 striated muscle, Skeletal muscles are composed of tubular ...

assembly. Other functions of nebulin, such as a role in

cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

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

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...

activity in a

calcium Calcium is a chemical element; it has 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 to it ...

calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all Eukaryote, eukaryotic cells. It is an intracellular target of the Second messenger system, sec ...

sensitive manner.

Mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

in nebulin cause some cases of the

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

disorder nemaline myopathy. A smaller member of the nebulin protein family, termed nebulette, is expressed in

cardiac muscle Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...

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 ph ...

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 The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...

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 importan ...

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 Skeletal muscle#Skeletal muscle cells, muscle fibers, and these cells contain ...

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 nemaline myopathy.

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