Cell division is one of the most critical periods of organ growth and
homeostasis. Cells in the body proliferate at different rates. Some divide
constantly and throughout life, like the ones that line the gut, whereas
others divide only rarely. Cell division is central to biology, but also to
disease.
Cell division is a high-fidelity physical process that ends with the
separation into two daughter cells, a process known as cytokinesis.
Cytokinesis, the separation of a cell into two daughter cells, initiates
with the strangling of the mother cell around the equator by the filaments
that form the cell’s skeleton. Next, cell shrinking at the equator as well
as centrifugal movement of the daughter cells induce the thinning of the
connection between the daughter cells. “It is like pulling apart two pieces
of a chewing gum that form a long, thin stretch of gum that eventually
breaks apart”, says Dr Miguel A. Valverde, head of the Molecular Physiology
Laboratory at UPF and leader of the project. The long, thin stretch of
plasma membrane and cytoplasm connecting the two daughter cells is called
the intercellular bridge and the final cut that results in two separate
cells is called abscission.
However, there is a major difference between the passive rupture of the gum
due to the mechanical force applied –pulling apart– and the fascinating
precision machinery of abscission. In the case of abscission, the thinning
of the intercellular bridge forms a tube of less than one micrometre (10-6
metres) in diameter with the objective of adapting its form and size to the
anchoring of the spring-like proteins –and their regulators– that strangle
the plasma membrane to generate two independent cells. “This final cut is a
critical step in cell division. It cannot occur too soon because the
daughter cells may not receive all the required information, nor too late
because the separating daughter cells may fuse again into a single cell but
with two nuclei, thereby acquiring an incorrect number of chromosomes, which
is known as aneuploidy –a significant characteristic of numerous kinds of
cancer”, affirms Dr. Cristina Pujades, principal investigator of the
Developmental Biology group at UPF.
Cancer is often the result of DNA mutations or problems with how cells
divide.
Since the discovery in the 19th century that cells divide, scientists have
tried to unravel the mechanisms operating in this high-precision process.
“We reasoned that during the formation of the intercellular bridge between
daughter cells there is tensioning of the plasma membrane that may activate
mechanosensitive ion channels”, says Dr. Julia Carrillo, first author of the
scientific publication.
Calcium entering the cell following the activation of Piezo1 promotes the
recruitment of the proteins forming the conical spring that strangles the
intercellular connection between daughter cells.
The UPF team found that during cytokinesis, the mechanosensitive Piezo1 ion
channel is almost uniquely activated at the intercellular bridge where it
generates a diffusible calcium signal. Moreover, they found that Piezo1 is
necessary for successful cytokinesis in different cell types, including the
endothelial cells that line the interior of the blood vessels, cells that
cure our wounds, breast cancer cells or in whole organisms such as zebrafish
embryos in which the activity of Piezo1 was reduced using genetic silencing
or a toxin obtained from a scorpion that specifically binds to the Piezo1
channel inhibiting its function.
Piezo ion channel proteins were identified in 2010 as fast sensors of
mechanical forces by this year Nobel Prize awardee, Ardem Patapoutian, and
soon after they were recognized as the molecules that our nervous system use
to sense touch. “Since their discovery, we and others have proposed that
Piezo channels are not only relevant to sense the world we live in but are
also used by cells to sense and react to their physical environment as they
are stretched, compressed, or move around within our body” affirms Dr.
Valverde.
Piezo1 is necessary for successful cytokinesis across different cell types
and species.
These findings lay the foundations for understanding this brief, dynamic
cell life stage that is critical for the growth and renewal of our organs
and pave the way for tackling the uncontrolled proliferation of cancer cells
in tumors by means of genetic or pharmacological regulation of the Piezo1
channel.
Reference:
Carrillo-Garcia J, Herrera-Fernández V, Serra SA, et al. The
mechanosensitive Piezo1 channel controls endosome trafficking for an
efficient cytokinetic abscission. Sci Adv. 7(44):eabi7785.
DOI: 10.1126/sciadv.abi7785
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