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Transcellular Calcium Transport in Mammary Epithelial Cells

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Abstract

The time-honored paradigm for mammary gland transepithelial calcium transport into milk is centered on the view that most, if not all, calcium enters milk through the secretory pathway, and no ionic calcium directly crosses the apical plasma membrane. Data from several recent studies all strongly suggest that most calcium, in fact, is extruded across the apical plasma membrane directly by the plasma membrane calcium-ATPase isoform 2 (PMCA2). In this review we break down transcellular calcium transport into the tasks of calcium entry, calcium sequestration and compartmentalization, and calcium extrusion. We compare and contrast the steps of calcium transport into milk by mammary epithelial cells, and the specific molecules that might perform these tasks, with well-characterized calcium transport mechanisms in other epithelia, such as the kidney, small intestine, and salivary gland. Finally, we suggest an updated model for calcium transport into milk that incorporates calcium transport across the apical plasma membrane.

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Abbreviations

CaM:

calmodulin

DAG:

diacylglycerol

ECF:

extracellular fluid

ER:

endoplasmic reticulum

ITP:

inositol-1,4,5-trisphosphate

ITPR:

ITP receptor

MEC:

mammary epithelial cell

NCX:

sodium/calcium exchanger

PLC:

phospholipase C

PMCA:

plasma membrane calcium-ATPase

PTH:

parathyroid hormone

PTHrP:

parathyroid hormone-related protein

SERCA:

sarco/endoplasmic reticulum calcium-ATPase

SPCA:

secretory pathway calcium-ATPase

TRP:

transient receptor potential

TRPC:

transient receptor potential canonical

TRPV:

transient receptor potential vanilloid

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VanHouten, J.N., Wysolmerski, J.J. Transcellular Calcium Transport in Mammary Epithelial Cells. J Mammary Gland Biol Neoplasia 12, 223–235 (2007). https://doi.org/10.1007/s10911-007-9057-1

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