Study Identifies Key Protein for Regulating Growth

Researchers in Germany have identified a key player in the complex process by which cells grow. Though fundamental to life, the mechanisms of growth are not fully understood but usually begin with cells doubling their components quickly so they can divide.

"In order for cells to grow, they have to produce lots of new proteins. This happens inside the cell in specialized factories called ribosomes," says Professors Utz Fischer from the Biocentre of the Julius Maximilian University of Würzburg (JMU). 

Up to ten million ribosomes are dedicated to this task in every human cell. Accordingly, cells spend a large part of their resources and energy reserves not only on the production of proteins, but above all on the production and maintenance of the ribosomes themselves. It is thought that up to 50% of the cellular energy reserve is required for this, making ribosome production the "most expensive" process in the cell.

Of course, the cell cannot afford to use up such large amounts of energy and raw materials senselessly. Therefore, it continuously monitors its environment to make sure that sufficient nutrients and other growth stimuli are available at all times. As soon as the "supply situation" deteriorates, it stops growing and shuts down the production of new ribosomes - but nevertheless keeps a sufficiently large supply of ribosomes on hand to be able to grow again without delay in better times.

The central command post in this process is the so-called mTORC1 signaling complex, a kind of nutrient sensor of the cell. "All information on the availability of nutrients and other growth stimuli converges at this signaling complex," says Dr. Cornelius Schneider, joint scientific collaborator of the two research labs and first author.

Based on this information, mTORC1 coordinates the cellular response to changing environmental conditions and controls the production of ribosomal proteins. As the researchers were able to show, it uses the help of another protein, LARP1. "mTORC1 can influence the LARP1 protein in such a way that, under nutrient deficiency, it binds to a signal sequence located at the beginning of the mRNAs of all ribosomal proteins. This leads to a reduction in protein production," says Schneider. mRNAs are, metaphorically speaking, the transporters of the blueprints for proteins from the cell nucleus to the ribosomes.

Although the production of ribosomal proteins is reduced to an absolute minimum, it is never completely shut down. "This means that the cell can start producing large quantities of ribosomes again at any time. This enables it to react extremely quickly to changing conditions and to switch from growth to energy saving," says Fischer. In this way, it is possible for the cell to always maintain a certain basic supply of mRNAs of the ribosomal proteins, even under poor conditions.

This also fits with another finding: LARP1 itself and the signaling network around mTORC1 are deregulated in different types of cancer, as they are at the center of the decision for or against cell growth.

The study was published recently in the journal Cell Reports.