Calmodulin and the Plasma Membrane Calcium Piimp*

Abstract

The data summarized and presented in this paper are consistent with the interpretation that CaM participates in the regulation of the plasma membrane calcium pump. Certain drugs, such as phenothiazines can antagonize CaM. Ca2+ loading of RBCs promotes CaM binding to RBC membranes and results in decreased responsiveness of the [Ca2+ + Mg2+)-ATPase to CaM. The latter effect may be mediated by a Ca2+ activated transglutaminase. Activation of (Ca2+ + Mg2+)-ATPase by CaM in vitro was shown not to be instantaneous, probably because of slow binding. CaM binding to isolated RBC membranes exhibits a Ca2+ dependence that is similar to that for activation of the (Ca2+ + Mg2+)-ATPase, and CaM binding does not decrease at high [Ca2+]s. Calculations based on assumed values for RBC [Ca2+], [CaM], and binding affinities of Ca2+ for CaM and CaM(Ca2+)n for the Ca2+ pump ATPase resulted in the tentative conclusion that most pump sites are occupied by CaM in the RBC in vivo. This conclusion, and the relatively slow time course of the CaM effect on (Ca2+ + Mg2+)-ATPase prompt us to suggest that, for all practical purposes, CaM is a subunit of the Ca2+ pump ATPase in vivo.

A Ca2+-stimulated adenosine triphosphatase in Golgi-enriched membranes of lactating murine mammary tissue

“…Exogenous calmodulin almost trebled the enzyme's specific activity and decreased its apparent Km for Ca2+ to 3 uM (Fig. 3b, *), a finding consonant with other reports (Scharff, 1979;Vincenzi et al, 1980). The conditions used for assaying the Golgi Ca-ATPase affected both the SR and calmodulinenriched RBC enzymes in a similar fashion, increasing their apparent affinities for Ca2+ and decreasing their maximum specific activities.…”

Evidence for a Calmodulin-Activated Ca2+ Pump ATPase in Dog Erythrocytes

“…Both enzymes were inhibited at higher Ca2+ concentrations. The Ca2+ activation profile of the (Ca2+ + Mg2+)-ATPase of human RBC membranes shows 50% activation at 7.0 X lop6 A4 Ca2+ and maximal activity at 4.0 X loe5 MCa2+ when the enzyme is activated by CaM (26). In the absence of CaM the Ca2+ profile does not have a maximum and tends to increase with increasing Ca2+ concentration.…”

Cellular function and pathological role of ATP13A2 and related P-type transport ATPases in Parkinson's disease and other neurological disorders

“…P-type ATPases also hold extended N- or C-terminal tails that regulate pump activity by intra-molecular interaction (Vandecaetsbeek et al, 2009) or via interaction of regulatory proteins (Vincenzi et al, 1980). The extensions may in addition control subcellular localization (Petris et al, 1998) or substrate delivery (Gourdon et al, 2011).…”