[HTML][HTML] Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia

WMT Groenestege, S Thébault… - The Journal of …, 2007 - Am Soc Clin Investig
WMT Groenestege, S Thébault, J van der Wijst, D van den Berg, R Janssen, S Tejpar…
The Journal of clinical investigation, 2007Am Soc Clin Investig
Our understanding of magnesium (Mg2+) regulation has recently been catapulted forward
by the discovery of several disease loci for monogenic disorders of Mg2+ homeostasis. In
this issue of the JCI, Groenestege et al. report that their study of a rare inherited Mg2+
wasting disorder in consanguineous kindred shows that EGF acts as an autocrine/paracrine
magnesiotropic hormone (see the related article beginning on page 2260). EGF stimulates
Mg2+ reabsorption in the renal distal convoluted tubule (DCT) via engagement of its …
Abstract
Our understanding of magnesium (Mg2+) regulation has recently been catapulted forward by the discovery of several disease loci for monogenic disorders of Mg2+ homeostasis. In this issue of the JCI, Groenestege et al. report that their study of a rare inherited Mg2+ wasting disorder in consanguineous kindred shows that EGF acts as an autocrine/paracrine magnesiotropic hormone (see the related article beginning on page 2260). EGF stimulates Mg2+ reabsorption in the renal distal convoluted tubule (DCT) via engagement of its receptor on the basolateral membrane of DCT cells and activation of the Mg2+ channel TRPM6 (transient receptor potential cation channel, subfamily M, member 6) in the apical membrane. These authors show that a point mutation in pro-EGF retains EGF secretion to the apical but not the basolateral membrane, disrupting this cascade and causing renal Mg2+ wasting. This work is another seminal example of the power of the study of monogenic disorders in the quest to understand human physiology.
The Journal of Clinical Investigation