For discoveries revealing the universal molecular machinery that orchestrates the budding and fusion of membrane vesicles — a process essential to organelle formation, nutrient uptake, and secretion of hormones and neurotransmitters.
This year's Lasker Basic Medical Research Award honors two scientists who discovered the universal molecular machinery that orchestrates the budding and fusion of membrane vesicles, a process that cells use to organize their activities and avert the biochemical anarchy that would result if all of their contents commingled. By 1970, George Palade had published his classic work showing that proteins travel between cellular compartments, but the molecular basis for this phenomenon was unknown. Using a biochemical and genetic approach, respectively, James Rothman and Randy Schekman transformed this descriptive field into one of detailed molecular clarity.
The cellular trafficking system they elucidated underlies numerous vital processes. Their discoveries explain, for example, how pancreatic cells release insulin, how nerve cells communicate, how embryos liberate growth factors to stimulate organ development, and how viruses infect. Alterations in these pathways explain a plethora of pathological processes, including the most common form of diabetes and the lethal effects of bacterial diseases such as botulism and tetanus. Scientists have developed drugs that target the trafficking system and are pursuing additional ways to pharmacologically manipulate it in an attempt to control an increasing number of illnesses, particularly those that relate to brain chemistry.
Award presentation by Michael Brown
Today, we honor Jim Rothman and Randy Schekman for unmasking the traffic signals that direct the assembly line of the cell. Each cell is a factory that manufactures thousands of proteins every minute and exports them to the outside world. These proteins are assembled in steps that must be performed in the proper order. To organize this assembly, cells use workstations specialized for each chemical reaction. This solves one problem but it creates another: how to transport partially finished proteins from one workstation to another, and how to make certain that each workstation has the right amount of energy, supplies, and worker enzymes.
The work stations are called organelles. They are like balloons filled with enzymes enclosed by a membrane. If you were reduced to microscopic size and were standing inside a human cell, you would be surrounded by hundreds of these organelles floating in space. Every so often, you would see a small bubble form on the surface of one organelle. The bubble is called a vesicle and its formation is called budding. The budding vesicle is filled with partially assembled proteins that must be carried to the next organelle. The vesicle detaches from its mother organelle and moves to a target organelle where it sticks like Velcro. Next the membranes between the vesicle and the organelle dissolve and the contents of the vesicle are injected into the organelle. This is called membrane fusion.
Interview with James Rothman and Randy Schekman