Null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2 impairs calcium transport into milk.
The means by which calcium is transported into the milk produced by mammary glands is a poorly understood process. One hypothesis is that it occurs during exocytosis of secretory products via the Golgi pathway, consistent with the observation that the SPCA1 Ca2+-ATPase, which is expressed in the Golgi, is induced in lactating mammary tissue. However, massive up-regulation of the PMCA2bw plasma membrane Ca2+-ATPase also occurs during lactation and is more strongly correlated with increases in milk calcium, suggesting that calcium may be secreted directly via this pump. To examine the physiological role of PMCA2bw in lactation we compared lactating PMCA2-null mice to heterozygous and wild-type mice. Relative expression levels of individual milk proteins were unaffected by genotype. However, milk from PMCA2-null mice had 60% less calcium than milk from heterozygous and wild-type mice, the total milk protein concentration was lower, and an indirect measure of milk production (litter weights) suggested that the PMCA2-null mice produce significantly less milk. In contrast, lactose was higher in milk from PMCA2-null mice during early lactation, but by day 12 of lactation there were no differences in milk lactose between the three genotypes. These data demonstrate that the activity of PMCA2bw is required for secretion of much of the calcium in milk. This major secretory function represents a novel biological role for the plasma membrane Ca2+-ATPases, which are generally regarded as premier regulators of intracellular Ca2+.
Periparturient Diseases of Cattle Research Unit, United States Department of Agriculture-Agriculture Research Service, National Animal Disease Center, Ames, Iowa 50010, USA. treinhar@nadc.ars.usda.gov
Timothy A
TA
Reinhardt
John D
JD
Lippolis
Gary E
GE
Shull
Ronald L
RL
Horst
D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000378:metabolism; D005089:Exocytosis; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism; D006579:Heterozygote; D007425:Intracellular Membranes / Q000378:metabolism; D007774:Lactation; D007785:Lactose / Q000378:metabolism; D008321:Mammary Glands, Animal; D051379:Mice; D018345:Mice, Knockout; D008861:Microsomes / Q000378:metabolism; D008892:Milk / Q000378:metabolism*; D009154:Mutation; D053499:Plasma Membrane Calcium-Transporting ATPases; D020033:Protein Isoforms; D013997:Time Factors; D015854:Up-Regulation
D027682:Cation Transport Proteins; D020033:Protein Isoforms; D053499:Plasma Membrane Calcium-Transporting ATPases; C506959:Atp2b2 protein, mouse; D000252:Calcium-Transporting ATPases; D007785:Lactose; D002118:Calcium