such as "Introduction", "Conclusion"..etc
Scientists used to think most of the exchange of information between
cells was conducted at the surface, where cell receptors receive signals
from other cells.
Now Yale researchers report in the March 20 issue of the journal Cell
how a switching station beneath the cell surface is crucial to
processing signals from outside the cell. They also describe a key
molecular switch that terminates signaling from this station.
The findings portray a much more "complex and fluid system of
cellular information processing than previously envisioned", said Derek
K. Toomre, assistant professor of cell biology at Yale and co-author of
The Yale team was led by Pietro De Camilli, M.D., the Eugene Higgins
Professor of Cell Biology and Neurobiology. De Camilli is also an
investigator in the Howard Hughes Medical Institute, a member of the
Kavli Institute for Neuroscience and a director of the Yale Program in
Cellular Neuroscience, Neurodegeneration and Repair.
When information arrives at the cell surface, receptors that decode
this information are internalized by a process called endocytosis.
Typically endocytosis was viewed primarily as a mechanism to turn off
signaling within the cell. However, recent research has shown signaling
continues after internalization and that its strength and quality is
strongly influenced by molecular interactions within the cell.
The signaling location characterized in the study, referred to as an
APPL1 endosome, plays a key role early in this signaling process. The
Yale team identified a molecular switch: the generation of a fatty
component (a phosphoinositide) in the endosome membrane that triggers
progression of receptors and other cargo from APPL1 endosomes to other
intracellular destinations. Turning off this switch jams traffic in the
APPL1 endosomes and enhances signaling.
De Camilli first became interested in this novel endocytic
compartment when studying a protein that binds to the APPL1 endosome and
is involved in Dent disease, a rare genetic disease of the kidneys, and
in Lowe syndrome, a rare genetic disease of the eyes, the kidneys and
"We expect that studies of APPL1 endosomes will not only advance our
understanding of basic mechanisms in cell physiology, but also give us
new insight about pathogenetic mechanisms and potential therapeutic
strategies in Lowe syndrome," De Camilli said.
Robert Zoncu and Rushika Perera, both postdoctoral associates at
Yale, were co first-authors of the study. Other Yale authors of the
paper are Daniel M. Balkin and Michelle Pirruccello.
The HHMI, the National Institutes of Health, the W.M. Keck
Foundation, the G. Harold and Leila Y. Mathers Charitable Foundation and
the Kavli Foundation funded the work.
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