Calponin 3. acidic is a

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, respo ...

that in humans is encoded by the ''CNN3''

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 ba ...

. The ''CNN3'' gene is located at 1p22-p21 in the human chromosomal genome. ''CNN3'' gene contains 7 exons and encodes calponin 3, a 36.4-kDa protein consisting of 329 amino acids with isoelectric point (pI) of 5.84. Calponin 3 is known as acidic calponin. Among three isoforms of calponin, less is known for the gene regulation and function of calponin 3. Nonetheless, much has been learned from extensive studies on the homologous genes ''CNN1'' and ''CNN2'' that encode calponin 1 and calponin 2.

Evolution

''CNN3'' is one of the three homologous calponin isoform genes. Calponin 3 is significantly diverged from calponin 1 and calponin 2 in the C terminal variable region. The higher degree of divergence among vertebrate ''CNN3'' genes than that in the ''CNN1'' and ''CNN2'' gene families suggests possibly earlier emergence of ''CNN3'', indicating that calponin 3 may represent a prototype of calponin ancestral of the three present-day isoforms (Fig. 1).

Structure-function relationships

The primary structure of calponin 3 is similar as that of calponin 1 and calponin 2, consisting of a conserved N-terminal calponin homology (CH) domain, a conserved middle region containing two actin-binding sites, and a C-terminal variable region. The unique length amino acid sequence of the C-terminal segment of the three calponin isoforms are responsible for their size and overall charge differences. Calponin 3 has been shown to participate in actin cytoskeleton-based activities such as that in embryonic development and myogenesis. Unlike calponin 1, calponin 3 has little effect on actomyosin Mg²⁺-ATPase activity and does not cause actin filaments bundling at the same condition as calponin 1 does.

Tissue distribution

Calponin 3 is found in the brain with expression in

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

astrocytes Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...

, and

glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...

, where it may function in regulating the actin cytoskeleton with a proposed role in the plasticity of neural tissues. Calponin 3 is also present in embryonic trophoblasts and

myoblasts Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development. Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called ''myotubes''. In the early development o ...

with functions in cell fusion during embryonic development and

myogenesis Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development. Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called ''myotubes''. In the early development o ...

Calponin 3 is also expressed in

B lymphocytes B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

Function

Calponin 3 was found in stress fibers of skin fibroblasts and myofibroblasts during wound healing. ''Cnn3'' knockdown in primary fibroblasts impaired stress fiber formation, resulting in decreased cell motility and contractile ability.> Calponin 3 in the brain has a potential function in regulating actin filaments during neuronal remodeling. Calponin 3 was also found in dendritic spines of adult hippocampal neurons to regulate dendritic spine plasticity. While mice with systemic knockout of ''Cnn1'' or ''Cnn2'', or both ''Cnn1'' and ''Cnn2'' survive to adulthood and fertile, systemic knockout of calponin 3 in mice results in embryonic and neonatal lethality due to defect in the development of central nervous system. ''CNN3'' was found in the trophoblasts of human placenta and plays a role of negative regulator of trophoblast fusion. Knockdown or dissociation of calponin 3 from cytoskeleton in response to PKC phosphorylation promoted fusion of trophoblasts. Consistently, calponin 3 was also present in myoblasts as an inhibitory regulator of cell fusion. Overexpression of calponin 3 in mouse C₂C₁₂ myoblasts inhibited cell fusion during ''in vitro'' differentiation, whereas ''Cnn3'' gene knockdown promoted cell fusion and the expression of skeletal muscle myosin. The inhibitory effect of calponin 3 was reversed upon phosphorylation by Rho-associated kinase 1/2 (ROCK1/2).

Notes

References

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