life depends on the ability of cells to adhere to one another. This
takes place through cell-cell junctions, protein complexes that
physically connect cells together. At the core of cell-cell junctions is
the protein cadherin, which spans across the cell membrane, sticking
out of the cell to connect to cadherins on neighboring cells.
also attaches to the internal cell cortex, a dense layer of proteins
underneath the cell membrane which has two major components: the
filament-forming protein actin that provides structural stability, and
the motor protein myosin that enables dynamic movement of the cortex
depending on the needs of the cell.
‘Cadherin clusters, which are well known for forming junctions between cells, also play a role in stabilising the cell cortex.’
This physical bridge between cells
enables the transmission of both mechanical and biochemical signals
across multicellular tissues.
However, scientists have observed
clusters of cadherin on the cell surface which are not involved in
cell-cell junctions. While it has been speculated that these
non-junctional and non-adhesive cadherin clusters are being kept in
reserve in order to strengthen or create new cell-cell junctions, the
actual function of these clusters remained unknown.
Scientists from the Mechanobiology Institute, Singapore (MBI) at the
National University of Singapore (NUS) have discovered that cadherin
play a role in stabilizing the cell cortex. The study was published in
the scientific journal Current Biology
expertise in cell adhesion and developmental biology, Principal
Investigator Assistant Professor Ronen Zaidel-Bar and Research Fellow Dr
Anup Padmanabhan of MBI used embryos from the nematode C. elegans
to probe the function of these non-junctional cadherin clusters. After
tagging the worm equivalent of cadherin, a protein named HMR-1, with a
fluorescent marker, they were able to follow its location and movement
by live imaging.
Focusing their investigation on the zygote, the
single fertilized egg cell that develops into an embryo, they discovered
that HMR-1 formed non-junctional, non-adhesive clusters similar to
cadherin. Even though these non-junctional HMR-1 clusters did not form
connections outside of the cell, they still remained internally
associated with actin filaments of the cell cortex, but not the myosin
motor proteins. In fact, the presence of non-junctional HMR-1 clusters
prevents cortical accumulation of myosin and decreases the contractile
activity of proteins that drive cortical movement.
In order to
determine whether non-junctional HMR-1 affected cytokinesis - the
physical process by which the cell cortex rotates and contracts to
divide the cell into two - the scientists genetically altered the level
of HMR-1. Reducing the amount of HMR-1 resulted in faster cytokinesis
while increasing HMR-1 levels slowed it down, demonstrating that these
non-junctional clusters have a key function in regulating movement of
the cell cortex.
Analysis of cortical dynamics during cell division
revealed that HMR-1 clusters attached to the actin filaments effectively
provided drag against cytoskeleton movement, by acting as structural
anchors lodged in the cell membrane. The importance of this anchoring in
maintaining cell integrity became clear following extended observation
of embryos with reduced levels of HMR-1, which were vulnerable to
cortical splitting, where a segment of cortex tears away from the cell
In essence, the non-junctional HMR-1 clusters can be
thought of as cellular staples that help secure the cortex to the cell
surface. The friction from the clusters stabilizes the cortex and slows
down cortical flow, preventing dramatic cortical deformation, while
allowing enough cortical movement for fundamental processes like
This new discovery means that scientists must
re-evaluate their understanding of cadherin. The importance of
non-junctional cadherin in stabilizing the cell cortex must now be
considered along with the classical function of cadherin in maintaining
cell-cell junctions. This fresh perspective may unlock new avenues of
investigation regarding the role of cadherin in health and disease.