Chromogranins from Cell Biology to Physiology and Biomedicine

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7 Effects of CGB Presence in the Cytoplasm and the Nucleus


The difference in the interaction property of CGA and CGB appeared to directly
influence the IP 3 -dependent Ca2+ mobilization effects of CGA and CGB; the effect
of CGB on the magnitude of IP 3 -dependent Ca2+ releases is substantially greater
than that of CGA even in the cytoplasm. The magnitude of IP 3 -mediated Ca2+
releases attributed to CGB in the cytoplasm is approximately twice as big as that
attributed to CGA, underscoring the critical importance of CGB in the IP 3 -dependent
Ca2+ signaling in the cytoplasm.
Differences in such effects have clearly been demonstrated by expressing chro-
mogranins in nonsecretory NIH3T3 cells that do not contain intrinsic chromogra-
nins (Fig.  4 ): CGA expression in NIH3T3 cells increased the IP 3 -induced Ca2+
release in the cytoplasm ~100% whereas CGB expression increased it ~200%
(Fig. 4A) (Huh et al. 2006a). On the other hand, suppression of CGA expression in
secretory PC12 cells that contain intrinsic chromogranins decreased the IP 3 -induced
Ca2+ release in the cytoplasm ~50% whereas suppression of CGB expression in
PC12 cells decreased the IP 3 -induced Ca2+ release ~75% (Huh et al. 2006a). Given
that chromogranin-containing cytoplasmic organelles include secretory granules
and the ER, the IP 3 -dependent Ca2+ mobilization effect of each chromogranin will
be through its IP 3 R/Ca2+ channel-modulatory role in these organelles.
In contrast, since there is no CGA in the nucleus, only CGB participates in the
IP 3 -dependent nucleoplasmic Ca2+ signaling. In line with the IP 3 R/Ca2+ channel-
activating role of CGB, the presence of CGB in the nucleus markedly enhanced the


Fig. 4 Effects of chromogranins on the IP 3 -induced Ca2+ release in the cytoplasm and nucleus of
NIH3T3 cells. The IP 3 -induced Ca2+ releases in the cytoplasm (A) and nucleus (B) of NIH3T3 cells
after transfection with CGA (CGA/ECFP) and CGB (CGB/ECFP) (Figure is modified from Fig. 2
of Ref. (Huh et al. 2006a))


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