| A 18-aa peptide sequence, mapping within cytoplasmic N-terminus of rat CaT-1/ECAC2 (1) was synthesized, coupled to KLH. Calcium (Ca+2 or Ca) is the most abundant cation and it is required for many physiological activities such as bone formation and it acts as a second messenger in signal transduction. However only 1% of Ca is present in ionic form in biological fluids. Ca concentration is regulated by calcitropic hormones that act on bone, kidney, and intestine. Extracellular Ca+-levels are sensed and regulated by Calcium Sensing receptor (CASR). When Ca levels are limiting then it must be taken up by active, transcellular pathways comprising (1) Ca++ entry across apical membrane, (2) cytosolic transport of Ca++ across the cell form apical to basolateral membrane facilitated by a family of low mol wt Calcium binding proteins (CABPs) that include vitamin D3-dependent Ca++ binding proteins (calbindin-D9k, Calbindin-28k, Calretinin, Parvalbumin, S100, calmodulin) and finally (3) an active extrusion of Ca++ through basolateral membrane mediated by Ca++-ATPase and Na+-Ca++ exchangers (NCX). Ca++ absorption in intestine and its reabsorption in kidney are carried out by Ca++ Transport (CaT) proteins, CaT-1, CaT-2 or Epithelial Ca Channel (ECAC1/ECAC2/CaT-Like (CaT-L) proteins. CAT1 (rat/mouse 727 aa, human 725 aa, chromosome 7q33-q34, ~85kD) is also known as ECAC2, CAT-like (CATL) or TRPV6 (transient receptor potential cation channel, subfamily V, member 6) contains a cytoplasmic N-terminus, 6 ankyrin repeat domains, 6 transmembrane domains, an extracellular pore region between TM5-6, and cytoplasmic C-terminus. CaT-1 shows 75% sequence identity to epithelial Ca++ channel (ECaC) protein from rabbit kidney. In rat, CaT-1 transcript (3-Kb) is expressed in duodenum, proximal jejunum cecum and colon but not in kidney, whereas ECaC in rabbit is expressed in apical cell membranes in distal part of nephron (kidney), duodenum, jejunum and placenta. The 6.5 Kb CaT-1-transcript in brain, thymus and adrenal gland and expressed sequences in rat and human brain and human prostate, spleen, placenta and lung suggest additional roles for CaT-1 beyond the intestinal Ca++ absorption. |
