Cell News 4/2014
12
Research news
et al., 2004; Gallo et al., 2007). Finally, it has been shown that
calcineurin is also involved in the development of heart valves
and coronary arteries (Liberatore and Yutzey, 2004; Yang et al.,
2014). The involvement of calcineurin in valve formation has
been studied in chicks and it has been shown that the level of
cardiovascular malformation depends on the timing and locali-
zation of calcineurin inhibition with CsA (Liberatore and Yutzey,
2004). Accordingly, for the development of coronary arteries the
authors found that calcineurin is involved in the development
of the arteries in a narrow time window (E12.5-E13.5) during
mouse embryogenesis, demonstrating a new spatiotemporal
role of the phosphatase (Yang et al., 2014).
The results show that more and more roles for calcineurin are
elucidated. However, as most of the publications used inhibitors
or calcineurin B knock-outs, not much is known about the im-
portance of the different calcineurin A isoforms. In mammals
three isoforms (
α, β, γ
) can be detected. CNA-
α
and -
β
are widely
expressed whereas expression of the
γ
-isoform is limited to the
testes and the brain (Rusnak and Mertz, 2000). It has already
been shown that specific isoforms are needed for specific de-
velopmental processes (Zhang et al., 1996; Bueno et al., 2002;
Gooch et al., 2004). However, more effort is needed to elucidate
the role(s) of all three isoforms in different cellular and develop-
mental processes. Also the spatiotemporal action of calcineurin
during development is only poorly understood and needs further
characterization.
In addition to mammals and chicks calcineurin has been inves-
tigated in some other animals. In
Caenorhabditis elegans
it has
Figure 1:
Schematic overview of the calcineurin signalling pathway. After an increase of the cytosolic Ca
2+
-concentration calmodulin is activated, which in turn can
activate calcineurin. Activated calcineurin dephosphorylates different target proteins. Calcineurin-targets are involved in developmental or other cellular
processes. ER = endoplasmatic reticulum.
