Submitted to: Biochemical and Biophysical Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 5, 2014
Publication Date: March 7, 2014
Citation: Reinhardt, T.A., Lippolis, J.D., Sacco, R.E. 2014. The Ca2+/H+ antiporter TMEM165 expression, localization in the developing, lactating and involuting mammary gland parallels the secretory pathway Ca2+ATPase (SPCA1). Biochemical and Biophysical Research Communications. 445(2):417-421. Interpretive Summary: We have previously shown that abrupt loss of calcium pumps at dry off, leads to accumulation of cell calcium and play a part in signaling mammary involution. Therefore loss of mammary calcium homeostasis is critical to initiation of rapid mammary involution and also mammary health. In this research we provide evidence for a new key protein that regulates important calcium pathways that are key to both lactation calcium support and mammary involution at dry off. Expression of this calcium transporter and its partners are likely key regulators of mammary involution during mastitis events and therefore require further study. These data are important to people studying the physiology and health of mammary tissues who seek new methods to control disease.
Technical Abstract: Plasma membrane Ca2+-ATPase 2 (PMCA2) knockout mice showed that ~ 60 % of calcium in milk is transported across the mammary cells apical membrane by PMCA2. The remaining milk calcium is thought to arrive via the secretory pathway through the actions of secretory pathway Ca2+-ATPase’s 1 and/or 2 (SPCA1 and 2). However, another secretory pathway calcium transporter was recently described. The question becomes whether this Golgi Ca2+/H+ antiporter (TMEM165) is expressed sufficiently in the Golgi of lactating mammary tissue to be a relevant contributor to secretory pathway mammary calcium transport. TMEM165 shows marked expression on day one of lactation when compared to timepoints prepartum. At peak lactation TMEM165 expression was 25 times greater than that of early pregnancy. Forced cessation of lactation resulted in a rapid ~50 % decline in TMEM165 expression at 24 hours of involution and TMEM165 expression declined 95% at 96 hours involution. It is clear that the timing, magnitude of TMEM165 expression and its Golgi location supports a role for this Golgi Ca2+ /H+ antiporter as a contributor to mammary Golgi calcium transport needs, in addition to the better-characterized roles of SPCA1&2.