Nebulette is a

cardiac The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

-specific

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some is ...

belonging to the

nebulin Nebulin is an actin-binding protein which is localized to the thin filament of the sarcomeres in skeletal muscle. Nebulin in humans is coded for by the gene ''NEB''. It is a very large protein (600–900 kDa) and binds as many as 200 actin monomers ...

family of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s. It is encoded by the ''NEBL''

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 ...

. This family is composed of 5 members: nebulette,

, N-RAP, LASP-1 and LASP-2. Nebulette localizes to Z-discs of

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 ...

and appears to regulate the length of

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 ...

thin filaments.

Structure

Nebulette is a 116.4 kDa protein composed of 1014 amino acids. As a member of the nebulin family of proteins, nebulette is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conserved S Dxx Y K motif. Like nebulin, nebulette has an acidic region with unknown structure at its N-terminus, and a serine-rich region adjacent to an

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 ...

at its C-terminus. Though nebulette shares structural features with nebulin, nebulin is expressed preferentially in

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...

and has an enormous size (600-900 kDa), while nebulette is expressed in

Z-disc 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 muscl ...

regions and is significantly smaller (roughly 1/6 of the size). Nebulette interacts with

tropomyosin Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons. Tropomyosin and the actin skeleton All organisms contain organelles that provide physical integrity to their cells. These type of organelles ...

, alpha-actinin. Xin, and XIRP2.

Function

Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic

cardiomyocyte 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 ...

s by

immunoprecipitation Immunoprecipitation (IP) is the technique of precipitating a protein antigen out of solution using an antibody that specifically binds to that particular protein. This process can be used to isolate and concentrate a particular protein from a sam ...

s with certain anti-nebulin

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

. Normal expression of nebulette is essential for the assembly and contractile function 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 myofi ...

s. Specifically, nebulette appears to regulate the stability and length of actin thin filaments, as well as beating frequencies of cardiomyocytes; reduction of full-length nebulette protein in cardiomyocytes resulted in reduced thin filament lengths, depressed beating frequencies and loss of thin filament regulatory proteins

troponin I Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I prevents myosin from binding to ac ...

and

Clinical significance

Mutations in the ''NEBL'' gene have been associated with

dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Co ...

. Studies in transgenic mice have supported their causative role in endocardial fibroelastosis and

References

External links

Mass spectrometry characterization of human NEBL at COPaKB
* {{Muscle tissue Proteins

Structure

Function

Clinical significance

Further reading

References

External links