Chemistry Reference
In-Depth Information
everything else that cells do in the intervening stages of life, including secretion, mobility, metabolic control,
synaptic plasticity, as well as the expression of numerous genes (for further details see
Berg et al., 2002; Carafoli,
Like Na
þ
, the extracellular concentration of Ca
2
þ
is much higher (20,000-fold) than in the cytosol of the average
mammalian cell. This is in sharp contrast with Mg
2
þ
, the concentration of which barely differs across the plasma
membrane. Since there is such a great discrepancy between the external and internal Ca
2
þ
concentrations
e
200 nMCa
2
þ
must be maintained to allow the signalling role of Ca
2
þ
fluxes
cytosolic levels of 100
it is clear that
to maintain intracellular Ca
2
þ
homeostasis, all cells must have developed mechanisms for regulating both Ca
2
þ
uptake and egress. However, there are at least three intracellular compartments which can accommodate much
higher Ca
2
þ
concentrations
e
e
the mitochondria, the endoplasmic reticulum, and the Golgi apparatus. Hence, most
of the Ca
2
þ
required by cells is not imported, but is released from these storage sites.
e
2D
AN OVERVIEW OF CA
REGULATION AND SIGNALLING
The way proteins function is determined by their shape and their charge. Ca
2
þ
binding to proteins triggers changes
in both shape and charge. Likewise, phosphorylation of the hydroxyls of Ser, Thr, or Tyr residues by protein
kinases (which represent about 2% of eukaryotic genomes) also changes protein charge, introducing a negative
charge, and also changes protein conformation. This ability of both Ca
2
þ
and phosphoryl groups to alter local
electrostatic fields and protein conformations are the two universal tools of signal transduction in biology.
The basic concepts of Ca
2
þ
regulation and signalling are summarised in
Figure 11.1
.
Ca
2
þ
-binding proteins
belong to two broad categories. The first are membrane transporters of Ca
2
þ
in the plasma membrane and in the
organelles, while the second, known as Ca
2
þ
-sensor proteins, decipher the Ca
2
þ
signal before transmitting it to
enzyme targets.
The basic concepts of Ca
2
þ
homeostasis.
FIGURE 11.1
(From
Carafoli, 2004
. Copyright 2004, with permission from Elsevier.)
