Johns Hopkins University. US: Just as human relationships are a two-way street, fusion between cells
requires two active partners: one to send protrusions into its neighbor,
and one to hold its ground and help complete the process. Researchers
have now found that one way the receiving cell plays its role is by
having a key structural protein come running in response to pressure on
the cell membrane, rather than waiting for chemical signals to tell it
that it’s needed. The study, which helps open the curtain on a process
relevant to muscle formation and regeneration, fertilization, and immune
response, appears in the March 9 issue of the journal Developmental Cell.
“We knew that in cell fusion, one cell attacks its fusion partner, but we didn’t know what the other cell was doing,” says Elizabeth Chen, Ph.D.,
an associate professor of molecular biology and genetics at the Johns
Hopkins University School of Medicine. “Now we know that the other cell
is putting up some resistance.”
The merging of two cells, which is crucial to conception, development
and physiology of complex organisms, was long thought to be a
symmetrical process, where two cells contribute equally. But two years
ago, Chen’s research group showed that, in fact, one of the fusion
partners initiates the process by extending fingerlike protrusions into the other partner.
For this study, Chen’s group and collaborators focused on the receiving
partner. Using fruit fly embryos and lab-grown fly cells that were
induced to fuse, they saw that in the areas where the attacking cells
drilled in, the receiving cells quickly fortified their cellular
skeletons, effectively pushing back. “We think that by stiffening its
skeleton in this way, the receiving cell avoids moving away from the
attacking cell, in which case fusion couldn’t occur,” Chen says. “The
interplay of the two cells pushing against one another brings the two
cell membranes into close proximity so that fusion can proceed.”
But how were the cellular skeleton’s building blocks, such as the
protein myosin II, being summoned to the fusion site? To find out,
Chen’s group altered cell surface proteins that are known to relay
chemical signals in the receiving cells of fly embryos. “In most of the
cells, we still saw myosin swarm to the fusion site, despite the fact
that chemical signaling had been disabled,” Chen says. In other words,
myosin is able to sense and respond to pressure on the outside of the
cell. Myosin’s “mechanosensory” response was also seen when Chen’s
collaborators used either a tiny pipette to apply a pulling force or a
tiny probe to apply a pushing force to lab-grown cells.
There is much still to learn about the cell fusion process, however.
Next, Chen’s group plans to examine how pressure is conveyed from the
cell membrane to its skeleton and which proteins on the membrane
facilitate fusion.
Other authors on the paper are Ji Hoon Kim, Yixin Ren, Shuo Li,
Yee-Seir Kee, Shiliang Zhang and Douglas N. Robinson of The Johns
Hopkins University; Win Pin Ng, Sungmin Son and Daniel A. Fletcher of
the University of California, Berkeley; and Guofeng Zhang of the
National Institute of Biomedical Imaging and Bioengineering.
The study was funded by the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (grant number R01AR053173), the
National Institute of General Medical Sciences (grant numbers
R01GM098816 and R01GM66817), the National Science Foundation (grant
number CMMI-1235569) and the Muscular Dystrophy Association.