Carriers, exchangers, and cotransporters in the first 100 years of the Journal of General Physiology

Transporters, pumps, and channels are proteins that catalyze the movement of solutes across membranes. The single-solute carriers, coupled exchangers, and coupled cotransporters that are collectively known as transporters are distinct from conductive ion channels, water channels, and ATP-hydrolyzing pumps. The main conceptual framework for studying transporter mechanisms is the alternating access model, which comprises substrate binding and release events on each side of the permeability barrier and translocation events involving conformational changes between inward-facing and outward-facing conformational states. In 1948, the Journal of General Physiology began to publish work that focused on the erythrocyte glucose transporter—the first transporter to be characterized kinetically—followed by articles on the rates, stoichiometries, asymmetries, voltage dependences, and regulation of coupled exchangers and cotransporters beginning in the 1960s. After the dawn of cDNA cloning and sequencing in the 1980s, heterologous expression systems and site-directed mutagenesis allowed identification of the functional roles of specific amino acid residues. In the past two decades, structures of transport proteins have made it possible to propose specific models for transporter function at the molecular level. Here, we review the contribution of JGP articles to our current understanding of solute transporter mechanisms. Whether the topic has been kinetics, energetics, regulation, mutagenesis, or structure-based modeling, a common feature of these articles has been a quantitative, mechanistic approach, leading to lasting insights into the functions of transporters.