Biology of Membrane Transport

This team focuses on the links between solute transport, metabolism and physiology, with an ongoing interest for proteins involved in transmembrane ammonium movements. The ammonium ion (NH4+) is an abundant and ubiquitous molecule on earth, serving as a major nitrogen source for micro-organisms and plants. In animals, ammonium is however mostly described as a cytotoxic metabolic product. Sophisticated ammonium detoxification and elimination pathways prevent its excessive accumulation. Hyperammoniaemia, as occurs upon liver failure for instance, has deleterious effects on the central nervous system function, leading to severe neurological symptoms and to death in acute cases. But in parallel to its cytotoxic effects, ammonium also plays a critical role in the regulation of the blood pH homeostasis, renal ammonium production and excretion into urine being a capital process to eliminate acid excess. The critical role of renal acid elimination is underscored by a variety of syndromes of tubular acidosis, chronic metabolic acidosis representing a mortality risk factor.

In spite of the potential important role that specific ammonium transport systems could play in the influx as in the efflux of this compound, it was assumed and taught since the forties that transmembrane ammonium transport is only carried out by passive diffusion of the neutral form NH3. Using yeast as a model, we identified and characterized specific ammonium transport proteins, thereby defining a new family highly conserved from microbes to invertebrates. We next unexpectedly found that the mammalian Rhesus factors (Rh) belong to this novel 'Mep-Amt-Rhesus' family.

Ongoing studies are seeking to identify connections linking a dysfunction in Mep-Amt-Rhesus proteins to human diseases. An in vivo characterization of the role of Mep-Amt-Rhesus proteins in the mouse and yeast physiology is tightly coupled to a detailed molecular analysis of the transport mechanism and gating regulation of these ammonium transport systems.