The Aging Process and Clathrin-Mediated Endocytosis in Yeast
Learn how aging affects nutrient delivery in yeast cells and the role of vacuoles.
Kenneth Gabriel Antenor, Jaime Lee-Dadswell, Nina Grishchenko, Shaimaa Swaleh, Allie Spangaro, Mojca Mattiazzi Usaj
― 5 min read
Table of Contents
Clathrin-mediated endocytosis (CME) is like a cellular delivery service. It helps cells pull in nutrients, proteins, and other essential stuff from the outside. Imagine it as a tiny vacuum cleaner that collects important materials from the outside world, helping cells to keep everything balanced and functioning properly.
CME is super important for all kinds of bodily functions. For instance, it plays a role in how immune cells present antigens, how nerve cells work, and even how cancer spreads.
Why Study Yeast?
Researchers often use a simple organism called budding yeast (that’s right, the stuff that makes your bread rise!) to understand complex processes like CME. Yeast cells are a bit like the guinea pigs of the science world-they’re easy to grow, and scientists have figured out a lot about how they work. By studying yeast, researchers can uncover new information about CME that might also apply to more complex cells in animals and humans.
How Does CME Work?
In budding yeast, CME is well-organized, involving a series of steps that happen in a specific order. First, certain proteins gather at precise locations on the cell’s outer layer, known as the plasma membrane. These spots are like designated pickup points for the cell's delivery service.
- Recruitment Phase: The first set of proteins, called the "early module," arrives and prepares the site for the operation.
- Coat Phase: Next, coat proteins show up to help round up the cargo and pull it in.
- Actin Assembly: Then, actin, a type of protein that helps in movement, comes into play to create a pulling mechanism.
- Final Assembly: Finally, the vesicle, which is sort of like a small bubble, is formed, containing all the goods collected by the cell.
As the process occurs, the cell has to be quite particular about the items it's collecting. If certain cargo isn’t present, the CME process can be delayed, like a delivery van waiting for customers to finalize their orders.
Aging and Its Effects on CME
Now, here comes the twist. Just like us, yeast cells age. As they get older, they tend to slow down. This aging influences the CME process, causing the cell to become less efficient at gathering the necessary nutrients and materials.
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Slower Operation: Older yeast cells take longer to form vesicles compared to younger ones. You can think of it like an older person trying to do the same tasks they used to do when they were younger-everything just takes a little longer!
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Impaired Function: Along with slower operation, older cells also have trouble recruiting the necessary proteins. Imagine the delivery team showing up late and not having the right equipment. That's how these aging yeast cells operate.
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Less Cargo: The amount of cargo that older cells manage to pull in is also reduced. It’s like having a kitchen that doesn’t have enough ingredients to make all the yummy dishes you want!
Vacuoles
The Role ofIn yeast, vacuoles act as storage compartments that surprise, surprise, help with maintaining balance in the cell. They keep things organized and prevent any unwanted buildup of materials.
As yeast ages, its vacuoles tend to lose their acidity, which is important for their function. If the vacuoles aren’t working properly, the whole system can go haywire. This loss of acidity has been linked to various problems, including the aging of cells.
V-ATPase Connection
TheOne critical player in maintaining vacuole acidity is a protein called V-ATPase. You can think of V-ATPase as a pump that keeps the vacuoles acidic, helping them work efficiently. Unfortunately, as yeast cells age, V-ATPase may not work as effectively, resulting in reduced acidity inside vacuoles.
When V-ATPase doesn’t do its job, the effects on CME can be significant. Think about it-if your delivery service can't access the right tools, how can they deliver? This is where the changes in vacuolar pH come into play.
The Impact of Caloric Restriction
Interestingly, there’s some good news! Researchers have found that reducing food intake, a process called caloric restriction, can help restore some of the functions lost during aging. This means that older yeast cells can improve their CME dynamics back to a more youthful state. It’s like giving your elder friend a nice diet to keep them spry!
When the yeast were given less sugar (but not too little!), their vacuoles regained their acidity and started performing better. This not only assisted the cells in gathering nutrients more effectively but also helped keep them healthier for longer.
TORC1 and NPR1
The Role ofNow let’s throw a couple more players into the mix: TORC1 and Npr1. These proteins help manage how well the cells respond to nutrients and control various aspects of the cell's behavior, including regulating CME.
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TORC1: This is like the manager of the protein delivery service. It helps ensure that the right decisions are made about protein activity in response to nutrient levels.
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Npr1: This little guy inhibits the action of alpha-arrestins, which are proteins necessary for tagging cargo for delivery. When TORC1 is not functioning well (like when vacuoles lose acidity), Npr1 can become less effective, leading to a drop in cargo delivery efficiency.
Without the proper functioning of these proteins, older yeast cells struggle to internalize nutrients effectively.
Conclusion
As yeast cells age, they become slow, and their internal delivery service for nutrients declines. Loss of acidity in vacuoles, inefficiencies in protein recruitment, and reduced activity from the crucial proteins TORC1 and Npr1 all contribute to these aging effects.
But like a good plot twist, caloric restriction can help rejuvenate these processes, making sure our yeast friends can still function well into their old age. So, the next time you enjoy a slice of bread, remember-there’s more going on in those yeast cells than you might think!
They age, they slow down, but with a little care, they can still deliver the goods.
Title: Vacuolar pH regulates clathrin-mediated endocytosis through TORC1 signaling during yeast replicative aging
Abstract: Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition and signalling. While cellular aging is associated with functional changes across many cellular components contributing to the collective decline in cellular function, little is known about how it affects CME. Here we show that CME dynamics are significantly altered during replicative aging in budding yeast, with older cells having slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced cargo internalization. This change in CME dynamics is mother cell-specific and is not observed in daughter cells. We identified vacuolar pH, a key driver of aging phenotypes in budding yeast, as a central player in this modulation of CME dynamics during aging. Perturbing vacuolar pH in young cells mimics aging-like CME dynamics, while maintaining an acidic vacuolar pH in aging cells preserves CME dynamics typical of young cells. Finally, we demonstrate that the vacuolar pH effect on CME is regulated through TORC1 via the effector kinase Npr1. These findings establish vacuolar pH as a critical regulator of CME during cellular aging, and strengthen its role in the overall cellular aging process in budding yeast.
Authors: Kenneth Gabriel Antenor, Jaime Lee-Dadswell, Nina Grishchenko, Shaimaa Swaleh, Allie Spangaro, Mojca Mattiazzi Usaj
Last Update: 2024-11-29 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.11.28.625547
Source PDF: https://www.biorxiv.org/content/10.1101/2024.11.28.625547.full.pdf
Licence: https://creativecommons.org/licenses/by-nc/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.