Paul Greengard
(1925 - )
Paul Greengard was born on December 11, 1925, in New
York City. During World
War II, he served in the United States Navy as a
electronics technician at the Massachusetts Institute
of Technology working on an early warning system to
detect Japanese kamikaze planes. After the war, he attended
Hamilton College where he graduated in 1948 with a bachelor's
degree in mathematics and physics. He decided against
graduate school in physics because most post-war physics
research was focusing on nuclear weapons, and instead
became interested in biophysics. He began his graduate
studies at Johns Hopkins University in the lab of Haldan
Keffer Hartline. Inspired by a lecture by Alan Hodgkin,
Greengard began work on the molecular and cellular function
of neurons. In 1953, Greengard received his PhD and
began postdoctoral work at the University of London,
Cambridge University, and the University of Amsterdam.
As a professor, he has worked at the Albert Einstein
College of Medicine, Vanderbilt University, Yale University,
and Rockefeller University.
In 2000, Greengard, Arvid Carlsson and Eric Kandel
were awarded the Nobel
Prize for Physiology or Medicine for their discoveries
concerning signal transduction in the nervous system.
Greengard's research has focused on events inside
the neuron caused by neurotransmitters. Specifically,
Greengard and his fellow researchers studied the behavior
of second messenger cascades that transform the docking
of a neurotransmitter with a receptor into permanent
changes in the neuron. In a series of experiments, Greengard
and his colleagues showed that when dopamine interacts
with a receptor on the cell membrane of a neuron, it
causes an increase in cyclic AMP inside the cell. This
increase of cyclic AMP, in turn activates a protein
called protein kinase A, which turns the function other
proteins on or off by adding phosphate groups in a reaction
known as phosphorylation. The proteins activated by
phosphorylation can then perform a number of changes
in the cell: transcribing DNA to make new proteins,
moving more receptors to the synapse (and thus increasing
the neuron's sensitivity), or moving ion channels to
the cell surface (and thus increasing the cell's excitability).
The following press release from the Royal Swedish
Academy of Sciences describes Greengard's work:
In the human brain there are more than hundred billion
nerve cells. They are connected to each other through
an infinitely complex network of nerve processes. The
message from one nerve cell to another is transmitted
through different chemical transmitters. The signal
transduction takes place in special points of contact,
called synapses. A nerve cell can have thousands of
such contacts with other nerve cells.
The three Nobel Laureates in Physiology or Medicine
have made pioneering discoveries concerning one type
of signal transduction between nerve cells, referred
to as slow synaptic transmission. These discoveries
have been crucial for an understanding of the normal
function of the brain and how disturbances in this signal
transduction can give rise to neurological and psychiatric
diseases. These findings have resulted in the development
of new drugs.
Paul Greengard, Laboratory of Molecular
and Cellular Science, Rockefeller University,
New York, is rewarded for his discovery
of how dopamine and a number of other transmitters
exert their action in the nervous system.
The transmitter first acts on a receptor
on the cell surface. This will trigger
a cascade of reactions that will affect
certain "key proteins" that in
turn regulate a variety of functions in
the nerve cell. The proteins become modified
as phosphate groups are added (phosphorylation)
or removed (dephosphorylation), which causes
a change in the shape and function of the
protein. Through this mechanism the transmitters
can carry their message from one nerve
cell to another.
Sources: Wikipedia,
Nobelprize.org
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