For a period of almost 15 years early in his career, Marc and I (R.J.L.) were very close collaborators, and up until the end our laboratories were adjacent to each other. Despite this very close, almost 50-year relationship, I must admit that it began with a deception. In 1972, when I was a clinical and research fellow at the Massachusetts General Hospital in Boston and publishing some of my early papers, Marc, then a graduate student, wrote inquiring about the possibility of doing postdoctoral work with me. He also emphasized that as a Canadian citizen he would qualify for a prestigious fellowship from the Medical Research Council of Canada. It was clear from his note that he did not appreciate that I was still a trainee myself but rather thought that I was a faculty member. Immediately recognizing his potential, and hoping that by a year hence I might in fact have landed a faculty job somewhere, I did nothing to disabuse him of this misconception. He got the fellowship, I got a job at Duke and, as they say, the rest is history. Marc’s early work focused on developing techniques for studying, purifying, and characterizing what are now known as G-protein-coupled receptors (GPCRs), using the β-adrenergic receptor as a model. He also contributed greatly to the discovery of the mechanisms by which receptor signaling is regulated by kinases and β-arrestins — in particular, how the β-arrestins are involved not only in desensitization but also in endocytosis and signaling. Early on, he developed a particular interest in dopaminergic signaling, which would lead to his laboratory’s developing tools for identifying, purifying and cloning the D1 and D2 receptors and clarifying their regulation and signaling mechanisms. In a classic paper, he defined an entirely new mechanism for regulation of behavior by D2 receptor signaling through β-arrestin.
However, his interests were not confined to postsynaptic mechanisms. Marc’s work also addressed many other key features of biogenic amine neurotransmission, and always with a view towards developing therapies for major brain and behavioral disorders. With the cloning and characterization of the dopamine transporter, his group illuminated the mechanisms by which it regulates behavior through elegant studies with knockout mice. These studies not only demonstrated dramatic changes in dopamine-mediated behaviors in the absence of the carrier, but also revealed remarkable adaptive changes in the expression of receptors, enzymes and signaling molecules as the system strains to cope with sustained elevation of extracellular dopamine.
