| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Nutrition, University of California Davis, Davis, California, United States
* To whom correspondence should be addressed. E-mail: slkelleher{at}ucdavis.edu.
Milk copper (Cu) concentration declines and directly reflects the stage of lactation. Three Cu-specific transporters (Ctr1, Atp7A and Atp7B) have been identified in the mammary gland; however, the integrated role they play in milk Cu secretion is not understood. While the regulation of milk composition by the lactogenic hormone prolactin (PRL) has been documented, the specific contribution of PRL to this process is largely unknown. Using the lactating rat as a model, we determined that the normal decline in milk Cu concentration parallels declining Cu availability to the mammary gland and is associated with decreased Atp7B protein levels. Mammary gland Cu transport was highest during early lactation, was stimulated by suckling and hyperprolactinemia which was associated with Ctr1 and Atp7A localization at the plasma membrane. Using cultured mammary epithelial cells (HC11), we demonstrated that Ctr1 stains in association with intracellular vesicles that partially co-localize with transferrin receptor (recycling endosome marker). Atp7A was primarily co-localized with mannose 6-phosphate receptor (M6PR, late endosome marker) while Atp7B was partially co-localized with protein disulfide isomerase (PDI, endoplasmic reticulum marker), TGN38 (trans-Golgi network marker) and M6PR. Prolactin stimulated Cu transport as a result of increased Ctr1 and Atp7A abundance at the plasma membrane. Although the molecular mechanisms responsible for these post-translational changes are not understood, transient changes in prolactin signaling plays a role in the regulation of mammary gland Cu secretion during lactation.
This article has been cited by other articles:
|
|
 |
|
  M. Moriya, Y.-H. Ho, A. Grana, L. Nguyen, A. Alvarez, R. Jamil, M. L. Ackland, A. Michalczyk, P. Hamer, D. Ramos, et al. Copper is taken up efficiently from albumin and {alpha}2-macroglobulin by cultured human cells by more than one mechanism Am J Physiol Cell Physiol, September 1, 2008; 295(3): C708 - C721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Michalczyk, E. Bastow, M. Greenough, J. Camakaris, D. Freestone, P. Taylor, M. Linder, J. Mercer, and M. L. Ackland ATP7B Expression in Human Breast Epithelial Cells Is Mediated by Lactational Hormones J. Histochem. Cytochem., April 1, 2008; 56(4): 389 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Linz, N. L. Barnes, A. M. Zimnicka, J. H. Kaplan, B. Eipper, and S. Lutsenko Intracellular targeting of copper-transporting ATPase ATP7A in a normal and Atp7b / kidney Am J Physiol Renal Physiol, January 1, 2008; 294(1): F53 - F61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lutsenko, N. L. Barnes, M. Y. Bartee, and O. Y. Dmitriev Function and Regulation of Human Copper-Transporting ATPases Physiol Rev, July 1, 2007; 87(3): 1011 - 1046. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
