'Fusion' Protein Found By Hopkins Researchers - Without It, Muscle Cells 'refuse

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'Fusion' Protein Found By s Hopkins Researchers - Without It,

Muscle Cells 'refuse To Fuse'

http://www.medicalnewstoday.com/medicalnews.php?newsid=67519

Working with fruit flies, scientists at s Hopkins have

discovered a protein required for two neighboring cells to fuse and

become one " super cell. "

Most cells enjoy their singular existence, but the strength and

flexibility of muscles relies on hundreds or even thousands of super

cells that make large-scale motion smooth and coordinated, such as

flexion of a bicep.

The newly discovered protein, dubbed Solitary, coordinates the

movement of tiny molecular delivery trucks to a cell's surface.

Cells that lack Solitary stay, well, solitary. " They refuse to

fuse, " says Hopkins assistant professor of molecular biology and

genetics Chen, Ph.D., whose report on the work is online

this week in Developmental Cell.

Chen and her team studied fruit fly embryo muscles to find the

molecular signals that tell two neighboring cells to join as one,

plucking out for further study those embryos containing cells that

refused to fuse.

They then compared the genetic sequences from healthy embryos with

sequences from defective embryos to locate differences and identify

the genes responsible for unfused muscle cells. In the process, they

identified Solitary.

Chen's team next made a tool to see the Solitary protein, enabling

them to track its localization under a fluorescent microscope. At

each future fusion point between cells that they examined in the fly

muscles, they saw concentrations of glowing clumps of Solitary

protein.

" As we uncover more of the players in cell fusion, we get closer to

manipulating fusion for our benefit, " Chen adds. Muscular dystrophy,

for example, might be treated by injecting into patients healthy

muscle cells that are designed to fuse efficiently with the diseased

muscles, saving the diseased cells from deteriorating.

They also discovered that Solitary protein is attached to the cell's

skeleton. " It was so bizarre to see Solitary - something meant to

regulate the cell's internal structure - to be involved in the

external events of cell fusion, " says Chen.

But in addition to structural support, the cell's " skeleton "

provides an internal railway of sorts, along which other proteins

and molecules can move. Indeed, the researchers saw that while

normal cells were able to shuttle tiny storage compartments within

the cell - presumably holding important molecular tools needed for

cell fusion - to the fusion site, these storage compartments were

scattered haphazardly, seemingly lost in the cellular wilderness, in

cells lacking Solitary.

When two neighboring cells fuse, they need to break down the barrier

between them, explains Chen. It turns out that the Solitary protein

marks where that break is happening and subsequently tells the cell

where to build its skeleton railway. " In this role, Solitary acts

not like the delivery truck, but more like a construction site

foreman, " says Chen. " It's told where the cell barrier needs to be

broken, then directs the building of a delivery road so that the

molecular supplies can be brought to the fusion site. "

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The research was funded by the National Institutes of Health, the

American Heart Association, the Mallinckrodt Jr. Foundation,

March of Dimes, Packard Foundation and Searle Scholars Program.

Authors on the paper are Sangjoon Kim, Khurts Shilagardi, Shiliang

Zhang, Hong, Sens, Jinyan Bo, Guillermo and

Chen, all of s Hopkins.

On the Web:

http://www.developmentalcell.com/

http://www.mbg.jhmi.edu/