Professor Bo Liu, Department of Plant
Biology, holds an Arabidopsis plant while Professor Jawdat Al-Bassam,
Department of Molecular and Cellular Biology, holds a model of the augmin
protein complex. Liu and Al-Bassam have worked out the structure of the augmin
complex, which plays a vital role in maintaining the protein skeleton in both
plant and animal cells. This could have applications both in human cancer and
infertility, and in breeding new varieties of crop plants. Credit: Joaquin
Benitez, UC Davis
Can the bend of a banana give us
insight into cancer? What does the shape of a rice grain have to do with
infertility? The proteins that give plants their shape and structure are also
involved in human disease. A team led by researchers at the University of
California, Davis, has mapped out the structure of a key player, augmin, in
exhaustive detail. Their work is published in the journal Nature Communications.
"This work shows how plants
and animals are similar," said Jawdat Al-Bassam, associate professor of
molecular and cellular biology at UC Davis. "It could help answer some
fundamental questions not just about plants, but also humans."
Augmin is a protein complex that
binds to microtubules, the cell's internal skeleton, aiding in the formation of
branched microtubules and playing a key role in cell division.
Augmin defects can cause
infertility in humans. In addition, "Some augmin subunits are highly
expressed in human cancer cells," said Bo Liu, a professor of plant
biology who collaborated with Al-Bassam on the new study. Understanding its
structure could yield both new medical treatments and new strategies for
breeding higher-quality rice and cotton crops.
A surprise in plants
Inside the cells of every plant and
animal is a shape-shifting skeleton.
This morphing skeleton can cause
cells to expand, stretch, or bend—sculpting the overall shapes of bulging
strawberries, curving cucumbers, and the long skinny nerve cells that connect
our brains and feet.
When a cell divides, its protein
skeleton grows long arms that reach out and grasp the DNA-containing
chromosomes. The arms then shorten, pulling the chromosomes apart, and ensuring
that each daughter cell receives a complete set of genes.
A cell's skeleton assembles from
tiny protein blocks called tubulin. The tubulin snaps together, creating hollow
rods called microtubules. These microtubules form the arms of a bigger
structure, called the spindle, which delicately separates the chromosomes when
a cell divides.
In 2007, scientists found that
animal cells could not form a functioning spindle if they lacked the augmin
protein complex. Without it, the microtubules could not branch, spindle arms
were weak and flimsy, and the cells often died during division.
"Most people did not think
augmin was also in plants," Liu said. But, in 2011, he and his
students discovered a set of eight augmin
genes in
Arabidopsis thaliana, a plant in the mustard family often used in genetic
research. Those plant genes encode a protein complex whose overall structure is
very similar to human augmin.
Cellular scaffolds, cotton and rice
Liu discovered that plant augmin
doesn't just assist cell division, as it does in animals; it also regulates the
shapes of plant cells.
As a plant cell grows, a scaffold
of microtubules expands within it. That scaffold positions enzymes at the
growing edges of the cell, allowing them to expand the rigid cellulose wall
that surrounds a plant cell.
When Liu reduced a cell's
production of augmin, its scaffold became flimsy and
disorganized.
"Microtubules guide the growth
of cells," he said.
This microtubule scaffold is
critical for plant survival; oryzalin, an herbicide frequently used on farms,
kills plants by interfering with it.
The scaffolding also shapes
important traits in crop plants. The juice in oranges is contained in gigantic
cells whose dramatic ballooning is driven by a microtubule skeleton that
expands inside each cell. Long-grained rice owes its shape to the microtubule
scaffolds that cause individual cells to elongate. It's also important in
cotton, whose fiber cells begin the size of a red blood cell and then extend,
driven by telescoping microtubules.
"It's pretty dramatic,"
Liu said. "They lengthen by thousands of times."
Even as Liu pieced together the
function of plant augmin, he knew almost nothing about how it physically
initiates branches in microtubules. So, he collaborated with Al-Bassam, who
worked upstairs in the same building, and who specializes in protein structures.
A molecular pitchfork
Md Ashaduzzaman, a postdoctoral
fellow in Al-Bassam's lab, cooled plant augmin proteins to -196° C and took thousands of electron
microscope images—an approach called CryoEM. He and Al-Bassam spent months
assembling the data into a single structure.
Their job was akin to that of
someone who had never seen the Eiffel Tower mapping its overall structure by
piecing together thousands of up-close photos.
They finally succeeded in unveiling
the mystery structure.
"Augmin turns out to look like
a pitchfork," said Al-Bassam. He and Ashaduzzaman worked out how the
pieces come together to form the complete augmin complex. They identified the
critical structures that it uses to attach to microtubules and form branches.
Seeing the nuanced differences
between the plant and animal versions of augmin could improve our understanding
of how it works on both sides.
In humans, altered levels of augmin
protein are associated with a worse prognosis in certain cancers of the liver,
brain and other organs. Understanding how augmin functions—or
malfunctions—could illuminate new ways to treat these cancers. It could also help
identify the unknown causes of infertility in some people.
Meanwhile, understanding how augmin
functions in plants could help scientists breed new varieties of important
California crops, such as plums and strawberries.
For Al-Bassam, it's a fulfilling
outcome.
"This was a very long endeavor," he said. "It was a real labor of love that required a lot of people working together."
Provided by UC Davis
Source: Plant cell structure could hold key to cancer therapies and improved crops
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