Tiny protein `squeezes' cells like balloon animals

Date:
August 4, 2021
Source:
University of Warwick
Summary:
A protein that causes a cell's skeleton to bend, allowing it to
twist the cell into different shapes, could be key to how cells
divide according to scientists.



FULL STORY ==========================================================================
A protein that causes a cell's skeleton to bend, allowing it to twist the
cell into different shapes, could be key to how cells divide according
to University of Warwick scientists.


==========================================================================
By making the cytoskeleton bend inwards to a tight point at its centre,
one cell divides into two -- much like how you would make a balloon animal
by twisting. The protein, named 'curly', has been observed bending the
material that makes up the cytoskeleton for the first time.

Their results, from research supported by the European Research Council
and Wellcome Trust, are published in the journal eLife and point to new
ways to modify and engineer cells, as well as a better understanding of
how they replicate -- a process essential to all living organisms.

All living matter is made up of cells, which are surrounded by a
fragile and flexible membrane much like a balloon. This is supported by
a cytoskeleton composed of a material called actin that give structure
and stability to cells.

Filaments of actin are semi-flexible and normally straight and it has
long been thought that they form structures by stacking together like matchsticks.

During cell division a cell will create a cytokinetic ring, a type of
machinery comprised of actin and motor proteins called myosin, along the
centre of the surrounding membrane. The myosins then constrict the actin filaments together and squeeze the cell down its middle until it divides
-- as if making the parts of a balloon animal, except from the inside.

Until now, it was thought that the actin filaments that comprise
the cytokinetic ring break up as the cell is squeezed tighter. An interdisciplinary collaboration between Professor Mohan Balasubramanian,
Dr Saravanan Palani (now at the Indian Institute of Science) and Dr Darius Ko"ster at the University of Warwick was astonished to find that a segment
of the protein Rng2, nicknamed 'curly', can naturally curve actin, with
10 micrometres of actin forming a ring less than a micrometre in diameter.



==========================================================================
It could suggest that 'curly' plays a key role in allowing the cytokinetic
ring to shrink tightly enough to divide a cell.

More than 20 years ago, Rng2 was discovered by one of the lead authors, Professor Mohan Balasubramanian, as an important protein in this process,
but only now have researchers made the astonishing observation that
it can bend actin filaments into actual rings. Rng2 is related to the
highly conserved IQGAP family of proteins present from yeast to human,
so the findings may be relevant to other cells as well, including human.

Lead author Dr Darius Ko"ster of Warwick Medical School said: "What we
show is if we have this protein on the membrane and we polymerise fresh
actin filaments at the membrane, representing what is happening in the cytokinetic ring, the actin starts to bend. If you have it in a cell,
it's a curved surface so the actin would curve.

"As far as we know, there are no other proteins doing this kind of job
with individual filaments. If you look inside cells, there are definitely curved actin structures, but it was thought that they were stacks of very
short straight filaments packed together. This opens the perspective that
it could be geometries and certain organelles that the actin is actually
wound around." The researchers used what is known as a reconstitution approach, in which they examine a complex system by separating it into
its constituent parts, then reassemble it to find out what role each
individual element plays.

For this study, that was funded by the European Research Council and
the Wellcome Trust, they made a lipid bilayer to represent the cell
membrane and experimented with adding different proteins to it that
are normally found at the interface with the cytokinetic ring during
cell division. They then added actin filaments and myosin to represent
the ring itself. It was when 'curly' was present that they observed the
actin forming highly curved structures, behaviour not normally seen in
these kinds of experiments.

It opens the possibility of using 'curly' as a tool to engineer different shapes of cells. Scientists could use it to modify the cytoskeleton and
twist the cell into new shapes, in a manner similar to balloon modelling.

Dr Ko"ster adds: "We have very few tools we can use to modify the cell
cortex and for the first time we have a way to engineer bent actin
structures. Since we can express it in cells and the cells react to it,
we can use it to modify what the cell cortex looks like.

"This can help us to really understand how curved actin can deform
membranes, or whether the cell uses this as a mechanism to control
certain processes.

There seem to be some proteins that like to twist and change the
curvature of actin and if that's happening then it's very likely that
there will be other proteins that take that as an information cue." ========================================================================== Story Source: Materials provided by University_of_Warwick. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Saravanan Palani, Sayantika Ghosh, Esther Ivorra-Molla, Scott
Clarke,
Andrejus Suchenko, Mohan K Balasubramanian, Darius Vasco Ko"ster.

Calponin-homology domain mediated bending of membrane-associated
actin filaments. eLife, 2021; 10 DOI: 10.7554/eLife.61078 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210804123543.htm

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