Molecular identification of ancient and modern mammalian magnesium transporters

Abstract

handling is poorly understood.The purpose of this review is to describe some of the recent insights into the identification and function of mammalian Mg 2ϩ transporters. There is a large body of physiological evidence for mammalian Mg 2ϩ transporters, which have only begun to be identified on the molecular level (11, 51,109,117,135,148,170). In particular, I will detail, at some length, the novel Mg 2ϩ transporters that have been identified over the last several years. These will be examined from the perspective of the established and more characterized mammalian Mg 2ϩ channels, mitochondrial Mrs2 and TRPM7/6. I will briefly review plant, bacterial, and yeast transporters as they relate to our newly identified mammalian Mg 2ϩ transporters, because some of these proteins share characteristics with the more ancient forms of transporters. The identification and characterization of plant, prokaryote, and yeast Mg 2ϩ transporters have been extensively reviewed elsewhere (35, 70, 73, 138).

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

“…This takes into account the fact that only 70% of total serum magnesium (30% is protein-bound) is available for glomerular filtration. Under normal conditions, 96% of filtered magnesium is reabsorbed in the renal tubules by several coordinated transport processes and magnesium transporters detailed below (9,12,(79)(80)(81)(82)(83)(84).…”

TRPM7 senses oxidative stress to release Zn 2+ from unique intracellular vesicles

“…However, as we have shown, Trpm7 −/− cells have normal total magnesium concentrations (3,14), with the many abundant magnesium transporters (20) probably accounting for normal Mg 2+ homeostasis. Under physiological conditions, plasma membrane TRPM7's inward conductance is miniscule (<10 pA/pF at −100 mV), but it increases over minutes if the free cytosolic Mg 2+ concentration falls below its normal level of ∼0.5-1 mM (21).…”

Mg2+-dependent Interactions of ATP with the Cystathionine-β-Synthase (CBS) Domains of a Magnesium Transporter

“…32 P]ATP (500 cpm/pmol) or [2, H]AMP (60 cpm/pmol) in the presence or absence of 10 mM MgCl 2 . The reaction systems were incubated for 20 min at 25°C and immediately filtered through nitrocellulose membranes (25-mm diameter, 0.22-m pore size; Millipore), which were prewashed with reaction buffer and washed with 1 ml of ice-cold reaction buffer.…”

“…The homeostasis of magnesium levels is strictly regulated by intestinal absorption and renal reabsorption, in which the epithelia function as a barrier that permits selective and regulated transport of Mg 2ϩ from apical to basolateral surfaces. Genomic analyses of familial cases of hypomagnesemia have identified key molecules directly involved in these processes (1,2). One of the least characterized members among these is the ancient conserved domain protein/cyclin M (CNNM) 3 family.…”