Researchers have identified a bacterial
protein that triggers a self-inflicted cell
death pathway in immune system cells
and could lead to a better understanding
of an important cellular structure.
The protein, RpsL, initiates a cascade
of events that leads the lysosome, a
cellular structure filled with enzymes
that break down and digest cellular
material, to open holes in its membrane
and release enzymes that destroy the
cell, says Zhao-Qing Luo, an associate
professor of biological sciences at
Purdue who led the research.
“Immune cells have various ways to
detect and defend against the presence
of pathogens or danger, and cellular
death induced by molecules from the
pathogens is a common way to fight
infection because it cuts off the stream
of nutrients and supplies to the pathogen,” Luo says.
“No one knows how the
selective release of the
enzymes within the lysosome
occurs, and no one had been
able to induce the process,” he
says. “Now we can. We know
that in the presence of this protein, holes open in the lysosome and enzymes are
released. This is a critical
ability needed to study lysosome function.”
Researchers identify a new trigger of CELLULAR SELF-DESTRUCTION
Researchers discovered a new protein involved in the process
that determines the fate of cells under stress and whether they
fight to survive or sacrifice themselves for the greater good.
A protein named H YPE orchestrates a response to misfolded
proteins within the cell, mistakes that increase when a cell is
under stress from disease or injury, says Seema Mattoo, an
assistant professor of biological sciences at Purdue University
who led the research.
Correct protein folding dictates the structure of a protein,
which is as important to its ability to function as the molecules
that make it up, she says. It also is critical in maintaining a stable environment within the endoplasmic reticulum, a structure
within the cell responsible for protein synthesis.
The cellular pathway that maintains this process in response
to stress is called the unfolded protein response, Mattoo says.
Like a person folding a pile of clothes fresh from the dryer,
proteins within the endoplasmic reticulum usually handle the
chore of protein folding neatly and methodically. Sometimes
mistakes are made and items need to be refolded. Usually, the
amount of refolding needed is manageable and efficiently finished, but stress on the cell leads to an increase in misfolded
proteins and, like the laundry, misfolded proteins can pile up.
Unlike the laundry, however, how well a cell keeps up with the
task of refolding proteins is a matter of life and death.
“If a cell is stressed and misfolded proteins begin to occur
more frequently, the cell tries to pick up the pace and refold the
proteins in an effort to survive,” Mattoo says. “If the stress is
sustained, more misfolds occur and eventually the cell can’t keep
up with the necessary refolding. At this point, a switch is flipped
that activates cell death. This isn’t always a bad thing, as it is
a mechanism that can help prevent the spread of infection and
offer benefits to the surrounding cells.”
The team next will study whether different stress signals
elicit different responses and will try to identify the signal that
PROTEIN determines life or death
fate of stressed cells
“There are hundreds of proteins for
which we have no idea what they do,”
she says. “Studying proteins is a little
like playing with Russian dolls. When you
investigate the role of one, it often leads
to another protein and something sig-
nificant about its role. It goes on and on,
and, as a researcher, I follow where it
Seema Mattoo, an assistant professor of
biological sciences, shows a slide of the
HYPE protein in human epithelial cells
on an inverted fluorescence microscope
designed for cell imaging.
(Photo by Charles Jischke)
A research team led by Zhao-Qing Luo, an associate professor of biological sciences
at Purdue University, identified bacterial protein RpsL
as a trigger of self-inflicted
cell death in macrophages.
(Photo provided by Laurie
Iten and Rodney McPhail)