Nav: Home

What the hair of a fly tells us about cancer

June 06, 2017

Things couldn't be simpler at the start: the cells divide into two identical cells that then divide in turn, meaning that any tissue can grow at an exponential rate. But the moment comes when some of them have to develop into specialised cells. On the back of a fly, for example, a cell must "know" that when it splits, it will give birth to two fundamentally different cells: one will make a hair and the other one, a neuron. How do these asymmetric divisions function? How can a mother cell split into two daughter cells that are so different? The researchers at UNIGE set about trying to understand these mechanisms down to the last detail, as the stakes are extremely high: a stem cell that misses out on its asymmetric division may generate cancer cells that reproduce exponentially, forming a tumour. You can read about the results of this research in Nature Communications, where the scientists demonstrate how the required information circulates inside the mother cell, enabling it to make a success of the asymmetric division.

In asymmetrical cell division, the two future cells "talk" to each other and divide their roles: "You'll become that, and I'll become this." They exchange information via proteins which carry the message. , These proteins are themselves contained in tiny vesicles, called endosomes. These endosomes act as a kind of cellular memory card: they are responsible for instigating the specialisation by migrating to one of the two daughter cells, where the information will be processed and subsequently transmitted to the sister cell. The key to this specialisation, therefore, lies in the ability of the endosomes to move to the left or right of the mother cell so that they are only present in one of the two daughters. But how do they go about this?

To analyse the phenomenon, the team led by Professor Marcos Gonzalez-Gaitan (from the biochemistry department in UNIGE's faculty of sciences) examined the hairs on the backs of flies, more precisely on fruit flies (Drosophila). These hairs are, in fact, sensory organs consisting of four cells, which are capable of picking up the force and direction of the wind: this is important to fly. Each hair -- or sensory organ -- originates from a single cell or SOP (sensory organ precursor), which first divides asymmetrically, producing two different cells, PIIA and PIIB. Each of these cells divides asymmetrically in turn, generating the four final cells. This is the ideal setting for attempting to understand how -- and why -- the endosomes move and make these asymmetric divisions possible.

Without Sara, nothing goes!

The first clue lies in the fact that the Sara protein is present in the endosomes, which helps them group together on the same side of the cell. When genetically-modified, mutant flies are deprived of the Sara gene -- and, by extension, of the protein that it produces -- the SOPs divide symmetrically and the hairs do not form; the flies, in other words, have naked backs without hairs. In the first phase of the research, Professor Gonzalez-Gaitan's team was able to show that the same process occurs in other types of cells, such as intestinal stem cells and even in the vertebrate nervous system, thanks to observations on fish.

Sara provides the crucial piece of information, therefore, that decides which daughter cell will receive the endosomes. However, this does not explain why they assemble in only one of the two daughter cells. More detailed observation was required to understand this mechanism. Microtubules inside the mother cell serve as tracks for transporting the endosomes, driven by a molecular motor called kinesin. The tracks are polarised (they are one-way-roads) and the kinesin always moves in the same direction. Some of the tracks lead to the left, others to the right, and the kinesin passes from one to the other, oscillating in the centre of the cell in a rapid sequence. Because there are more tracks pointing to one cell, at the end the endosomes, with the key message in them, are sent towards the right cell. But at the end, the endosomes need to scape from the trap to be delivered to the PIIA cell, which will make the hair. How?

On the right track

To escape from this trap and to allow the endosomes to gather on the proper side, it is essential not only that the Sara protein is present, but also that it is bound to a molecular extension known as a phosphate group. Professor Gonzalez-Gaitan and his team succeeded in demonstrating the key role played by this phenomenon. Known as phosphorylation, it acts like a central switch signalling the start of the final migration of the endosomes to be released to the right cell. Without this process, the information could not circulate between cells, which would then prevent any differentiation between the two daughter cells... condemning the flies to everlasting baldness! Anomalies in the way these fascinating molecular phenomena function in the cells lies behind the emergence of certain cancer tumours in humans.

Université de Genève

Related Protein Articles:

Hi-res view of protein complex shows how it breaks up protein tangles
A new, high-resolution view of the structure of Hsp104 (heat shock protein 104), a natural yeast protein nanomachine with six subunits, may show news ways to dismantle harmful protein clumps in disease.
Breaking the protein-DNA bond
A new Northwestern University study finds that unbound proteins in a cell break up protein-DNA bonds as they compete for the single-binding site.
FASEB Science Research Conference: Protein Kinases and Protein Phosphorylation
This conference focuses on the biology of protein kinases and phosphorylation signaling.
Largest resource of human protein-protein interactions can help interpret genomic data
An international research team has developed the largest database of protein-to-protein interaction networks, a resource that can illuminate how numerous disease-associated genes contribute to disease development and progression.
STAT2: Much more than an antiviral protein
A protein known for guarding against viral infections leads a double life, new research shows, and can interfere with cell growth and the defense against parasites.
A protein makes the difference
It is well-established knowledge that blood vessels foster the growth of tumors.
Nuclear protein causes neuroblastoma to become more aggressive
Aggressive forms of neuroblastoma contain a specific protein in their cells' nuclei that is not found in the nuclei of more benign forms of the cancer, and the discovery, made through research from the University of Rochester Medical Center, could lead to new forms of targeted therapy.
How a protein could become the next big sweetener
High-fructose corn syrup and sugar are on the outs with calorie-wary consumers.
High animal protein intake associated with higher, plant protein with lower mortality rate
The largest study to examine the effects of different sources of dietary protein found that a high intake of proteins from animal sources -- particularly processed and unprocessed red meats -- was associated with a higher mortality rate, while a high intake of protein from plant sources was associated with a lower risk of death.
Protein in, ammonia out
A recent study has compiled and analyzed data from 25 previous studies.

Related Protein Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...