Calponin 3, acidic

Figure 1. Evolutionary lineage of vertebrate calponin 3 isoforms deduced from alignment of amino acid sequences.

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).

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[7] and myogenesis.[8] 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.[9]

Calponin 3 is found in the brain with expression in neurons,[10][11] astrocytes,[12] and glial cells,[13] where it may function in regulating the actin cytoskeleton with a proposed role in the plasticity of neural tissues.[14][15] Calponin 3 is also present in embryonic trophoblasts and myoblasts with functions in cell fusion during embryonic development and myogenesis[7][8] Calponin 3 is also expressed in B lymphocytes.[16]

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.[8]> Calponin 3 in the brain has a potential function in regulating actin filaments during neuronal remodeling.[17] Calponin 3 was also found in dendritic spines of adult hippocampal neurons to regulate dendritic spine plasticity.[15] While mice with systemic knockout of Cnn1[18] or Cnn2,[19] 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.[16] 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.[7]

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).[7]