Plasma membrane Ca2+ ATPases are single polypeptides of about 1,100 to 1,250 amino acid residues with a molecular mass of 125 to 140 kDa. They contain 10 membrane spanning segments and their N- and C-termini are both on the cytosolic side. The bulk of their mass is also in the cytoplasm and contains three major intracellular domains: the A (actuator), the N (nucleotide-binding) and P (catalytic phosphorylation) domains. Four basic isoforms are encoded by four distinct genes and their transcripts originated a huge number of alternative splicing variants that in most cases are also translated in the corresponding protein variants. Emerging evidence underlines that PMCA pumps, in addition to maintain resting cytosolic Ca2+ levels against a steep concentration gradient (i.e., nM versus mM) play a local control in specific sub-plasma membrane domains by tethering Ca2+/calmodulin dependent enzymes and reducing their activity, i.e., by decreasing Ca2+ concentration in the microenvironment where they are confined. This aspect of pump activity confers to PMCA pump a key role as signal transducer and justifies the existence of so many PMCA variants that could be specialized in tuning the activity of different partners with different Ca2+ sensitivity.
The plasma membrane Ca2+ ATPases: isoforms specificity and functional versatility
CALI', TITO;OTTOLINI, DENIS;BRINI, MARISA
2016
Abstract
Plasma membrane Ca2+ ATPases are single polypeptides of about 1,100 to 1,250 amino acid residues with a molecular mass of 125 to 140 kDa. They contain 10 membrane spanning segments and their N- and C-termini are both on the cytosolic side. The bulk of their mass is also in the cytoplasm and contains three major intracellular domains: the A (actuator), the N (nucleotide-binding) and P (catalytic phosphorylation) domains. Four basic isoforms are encoded by four distinct genes and their transcripts originated a huge number of alternative splicing variants that in most cases are also translated in the corresponding protein variants. Emerging evidence underlines that PMCA pumps, in addition to maintain resting cytosolic Ca2+ levels against a steep concentration gradient (i.e., nM versus mM) play a local control in specific sub-plasma membrane domains by tethering Ca2+/calmodulin dependent enzymes and reducing their activity, i.e., by decreasing Ca2+ concentration in the microenvironment where they are confined. This aspect of pump activity confers to PMCA pump a key role as signal transducer and justifies the existence of so many PMCA variants that could be specialized in tuning the activity of different partners with different Ca2+ sensitivity.
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