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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive Dec 6, 2013

 

If a yeast mating attempt fails, the unsuccessful yeast cell develops a molecular memory of the event. The protein Whi3 becomes inactive. Once inactive, Whi3 "contaminates" other proteins of its same type. These proteins attach themselves to each other forming aggregates, which the yeast cell can only break apart with great difficulty.

Whi3 aggregates ensure that future "lovers" have to release a much larger amount of the pheromone attractant for that yeast cell to respond. If the amount is too low, the yeast cell continues to reproduce solely through asexual budding.







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What yeast teach us about memory formation

Yeast cells are able to form a memory by combining proteins.

Yeast has a somewhat complicated love life. On one hand, a mother cell can produce genetically identical daughter cells through mitosis (cell division). On the other hand, yeast cells, who exist in two different mating types, are able to fuse with cells of the other mating type, thereby combining two different sets of genes.

Two yeast cells — a single chromosome set resides in each yeast cell — become a so-called "yeast zygote" with two sets of chromosomes.

To enable two fusion-inclined yeast cells to approach each other, each mating yeast type releases a certain pheromone. If mating yeast then detect each other, they cease asexual cell division, and cast a special extension towards each other in a kind of courtship. If these extensions meet, the cells fuse and form a zygote. If the partners miss, however, they both carry on producing offspring asexually through budding.

The work is published in Cell magazine.

Unexpected memory

ETH-Zurich researchers Fabrice Caudron and Yves Barral, a professor of biochemistry, have now discovered a previously unknown mechanism that enables yeast cells to memorise "bad experiences" during reproduction.


If a mating attempt proves fruitless, the unsuccessful yeast cell develops a molecular memory — the protein Whi3 is transformed and becomes deactivated.

Once deactivated, Whi3 "contaminates" other proteins of its same type. These proteins attach themselves to each other forming aggregates, which the yeast cell can only break apart with great difficulty.

Whi3 aggregates can only be broken if future "lovers" release a much larger amount of the messenger substance inducing the yeast cell to respond.

If the amount is too low, the cell continues to reproduce solely through budding.


"Nobody expected to find such a memory in a single-celled organism," explains Yves Barral, stressing the singularity of the discovery. Interestingly, there is a connection between memory and aging. As the cell grows older, the memories accumulate in a cell in the form of these aggregates. "Finding a suitable sexual partner becomes increasingly more difficult with time," says the ETH Zurich professor.

After all, the aggregation process is extremely difficult to reverse. Only very rarely is the memory lost when the cell manages to dismantle the aggregates.


The daughter cells that a mother cell pinches off do not inherit the memory and the aggregates remain in the mother.

As a result, the offspring are not predisposed as the daughter cell is young.

How the mother cell retains the protein aggregates is an important mechanism, which Barral and Caudron are currently researching.


Memory conserves energy

Research still needs to be conducted into why yeast cells store these (and other) substances. "A memory could thus be useful for the yeast to prevent further unproductive yet energy-intensive mating attempts," says Caudron, who has been researching this phenomenon for the last six years. The yeast faces a dilemma: if it only forms clones, the population will be genetically homogenous and, for instance, could die out in the event of a sudden change in the environmental conditions.

While sexual reproduction leads to a more genetically varied population, the trade off is that cells have to expend far more energy to break up "memory" protein agregates.

"Cheating" yeasts are then a problem. If another cell or even a foreign organism produces the pheromone without offering a mating opportunity, a naïve cell would wait in vain for its supposed partner without dividing through budding in the meantime. This would rule it out as a competitor for nutrients – much to its own detriment.

Yet, it is only worth responding to pheromones if successful reproduction is guaranteed. A yeast cell only stands a chance of producing a 'zygote' if the pheromone is present at high concentrations. This signal indicates the immediate proximity of a partner worthy of fusion.

From bacteria to multicellular organisms

With this work, the ETH Zurich scientists demonstrated a form of non-hereditary memory in a single-celled organism for the first time.


The system of protein aggregates, appears to be universal and relatively old in the history of evolution. Barral also knows of bacteria that grow "old" similarly to yeast cells. He suspects these bacteria could have a similar memory mechanism.

One such mechanism has also been detected in the fruitfly, Drosophila. Males perform a courtship dance to win the affection of a female. If she has already been fertilised, she does not show any interest. The male memorises this experience in nerve endings, synapses, with the aid of protein aggregates.


For Barral and Caudron, this is an indication that memory processes are very similar in single and multicellular organisms. "Who would have thought that a single-celled organism like yeast could help us to understand how we memorise our experiences?" says Barral.

Abstract
Highlights
Yeast cells unproductively exposed to pheromone enter a pheromone refractory state
The refractory state is memorized by mother cells, not inherited by daughter cells
Memory is encoded by super-assembly and inactivation of the mRNA-binding protein Whi3
Whi3 is a mnemon, i.e., protein-establishing memory through its super-assembly

Summary
Cellular behavior is frequently influenced by the cell’s history, indicating that single cells may memorize past events. We report that budding yeast permanently escape pheromone-induced cell-cycle arrest when experiencing a deceptive mating attempt, i.e., not reaching their putative partner within reasonable time. This acquired behavior depends on super-assembly and inactivation of the G1/S inhibitor Whi3, which liberates the G1 cyclin Cln3 from translational inhibition. Super-assembly of Whi3 is a slow response to pheromone, driven by polyQ and polyN domains, counteracted by Hsp70, and stable over generations. Unlike prion aggregates, Whi3 super-assemblies are not inherited mitotically but segregate to the mother cell. We propose that such polyQ- and polyN-based elements, termed here mnemons, act as cellular memory devices to encode previous environmental conditions.

Authors
Fabrice Caudron, Yves Barralsend emailSee Affiliations

Further reading

Caudron F & Barral Y. A Super-Assembly of Whi3 Encodes Memory of Deceptive Encounters by Single Cells during Yeast Courtship, Cell (2013) online publication 5th December 2013. DOI: http://dx.doi.org/10.1016/j.cell.2013.10.046