Prokaryotic ammonium transporters: what has three decades of research revealed?

The exchange of ammonium across cellular membranes is a fundamental process in all domains of life. In plants, bacteria and fungi, ammonium represents a vital source of nitrogen, which is scavenged from the external environment. In contrast, in animal cells ammonium is a cytotoxic metabolic waste product and must be excreted to prevent cell death. Transport of ammonium is facilitated by the ubiquitous Amt/Mep/Rh transporter superfamily. In addition to their function as transporters, Amt/Mep/Rh proteins play roles in a diverse array of biological processes and human physiopathology. Despite this clear physiological importance and medical relevance, the molecular mechanism of Amt/Mep/Rh proteins has remained elusive. Crystal structures of bacterial Amt/Rh proteins suggest electroneutral transport, whilst functional evidence supports an electrogenic mechanism. Here, focusing on bacterial members of the family, we summarize the structure of Amt/Rh proteins and what three decades of research tells us concerning the general mechanisms of ammonium translocation, in particular the possibility that the transport mechanism might differ in various members of the Amt/Mep/Rh superfamily.