Biology Reference
In-Depth Information
calcium gradient to restore luminal ER calcium levels ( Guerrero-Hernan-
dez et al., 2010 ). Small proteins, such as phospholamban and sarcolipin,
modulate SERCA activity according to cellular requirements and/or extra-
cellular signals ( Periasamy and Kalyanasundaram, 2007 ; Brini and Carafoli,
2009 ; Guerrero-Hernandez et al., 2010 ).
Distinct genes code for the three different pumps, SERCA 1, 2 and 3,
generating a total of 10 isoforms by alternative splicing. SERCA1 is expressed
principally in skeletal muscle, with two known isoforms, SERCA1a (adult)
and SERCA1b (fetal). SERCA2a is mainly expressed in cardiac and skeletal
muscle, while SERCA2b and SERCA3 are present in nonmuscle cells, the
latter being the most ubiquitous of the isoforms ( Periasamy and Kalyana-
sundaram, 2007 ; Brini and Carafoli, 2009 ).
2.2.2.2. Ryanodine Receptor
RyR is an ER and SR calcium channel important for regulation of calcium
transients in excitable cells. Three isoforms of this receptor are known to
exist, RyR1, 2 and 3; RyR1 is mainly present in skeletal muscle, RyR2 in
cardiac muscle, and RyR3 in nerve fibers and in nonexcitable cells ( Marks,
2001 ; Zalk et al., 2007 ).
RyR conductance is governed by several proteins, such as voltage-gated
channels (Cav 1.1/Cav 1.2 or dihydropyridine receptor), protein kinases
(PKA and CaMKII), calcium-binding proteins (Calmodulin and Calseques-
trin) and the FKBP-12 and 12.6 proteins ( Lanner et al., 2010 ). Also, divalent
cations, such as calcium and magnesium, and nucleotides, such as ATP, are
other important regulators of RyR ( Lanner et al., 2010 ). In addition, RyRs
possess a series of sulfhydryl and cysteine groups sensitive to the redox state
of the cell ( Sun et al., 2008 ; Donoso et al., 2011 ).
2.2.2.3. IP3R
The IP3R is a tetrameric protein that transports calcium from the ER into
the cytoplasm. It is responsible for calcium transients in nonexcitable cells,
nuclear calcium regulation and calcium transfer between ER and mito-
chondria ( Taylor and Tovey, 2010 ).
The IP3R requires elevated calcium levels to be activated by its agonist,
IP3. IP3 binds to the IP3R at four sites in a cooperative manner. In parallel,
calcium regulates IP3 function through calcium-binding sites, which are
different from those used for ion transport. Depending on the calcium con-
centration, IP3Rs possess a two-phase response. Low amounts of calcium
increase the IP3R response, independent of IP3 levels. On the contrary,
Search WWH ::




Custom Search