Asymmetry due to perfect balance

Apr 25, 2007
Cortical Polarity in a Yeast Cell
A) Cortical polarity in a yeast cell: Fluorescent Cdc42 molecules form a cap in the membrane of a yeast cell (arrow). A fluid-filled vacuole inside the cell appears as a white circle. The white bar indicates two micrometres. B) Schematic model of cortical polarity and its molecular mechanisms: diffusion (double sided arrows), active transport (arrows towards the plasma membrane) and endocytosis (arrows away from the plasma membrane). Taken together they allow the accumulation of Cdc42 molecules (blue circles) and the creation of a cap. Credit: Max Planck Institute of Biochemistry

Cell membranes are like two-dimensional fluids whose molecules are distributed evenly through lateral diffusion. But many important cellular processes depend on cortical polarity, the locally elevated concentration of specific membrane proteins.

Roland Wedlich-Soldner at the Max Planck Institute of Biochemistry in Martinsried, Germany, and his colleagues at Harvard Medical School, Boston, The Stowers Institute for Medical Research, Kansas City, and the University of Texas Southwestern Medical Center, Dallas, have analysed and quantified how cortical polarity develops and how an asymmetric distribution of molecules can be dynamically maintained. In their study they combined experiments on living cells with a mathematical model to show among other things that polarised regions in membranes are defined with nearly optimal precision. This novel approach is an important step towards a spatially and temporally quantifiable model of the cell.

Cortical polarity is a prerequisite for a variety of cellular processes like cell division, local cellular growth, the secretion of substances and many steps in the embryonic development of organisms. To establish an asymmetric distribution of membrane proteins, diffusion has to be countered for a long enough time to allow the molecules to accumulate and fulfill their functions. This is possible through active and directed transport whose net effects need to outdo diffusion till the necessary concentration of molecules is reached.

"We wanted to know which principles allow the establishment and maintenance of cortical polarity - and to quantify their respective roles," says Wedlich-Soldner. Apart from diffusion which prevents locally elevated concentrations of molecules there are only two other cellular mechanisms that influence the distribution of membrane proteins. The already mentioned active transport processes rely on structures of the cytoskeleton to move molecules or whole organelles in specific directions. The process of endocytosis, on the other hand, allows cells to absorb membrane molecules by forming vesicles out of small portions of the cell membrane.

For their study the research team used a well-characterised model system: Budding yeast cells expressing activated Cdc42, a central regulator of cortical polarity. Mutations in Cdc42 can hinder the establishment or maintenance of cell polarity and thus lead to the development of cancer. As so-called oncogenes some of the protein’s activators have also been shown to cause tumour growth.

The asymmetric distribution of Cdc42 in the cell membrane creates an area with elevated concentrations of that molecule, which is defined as a cap. This site is used as a marker for the growth of a daughter cell during cell division. To establish a cap Cdc42 molecules have to accumulate in a small region of the cell membrane and it is important that this area is defined with high precision. The new data show that this is achieved mainly through endocytosis.

This process internalises parts of the plasma membrane through small vesicles - in the process removing Cdc42 as well. As Cdc42 in the centre of a cap is replenished through directed transport, endocytosis mainly leads to a sharpening of the cap edges. "We’ve seen for the first time how cells are able to establish caps with near perfect spatial precision", says Wedlich-Soldner. "It looks almost like a cut-off."

Taken together the results show that a balance of diffusion, active transport and endocytosis is enough to describe the process of cortical polarity with exceptionally high accuracy. "Our model system is rather simple and therefore especially suitable for analysis", says Wedlich-Soldner. "It enabled us to describe and quantify the roles of these three important mechanisms for the first time on a systemic level and with the help of a single mathematical model. Our data represent an important step towards a better understanding of the principles of how biological systems establish asymmetric distribution of molecules in a dynamic and precise way."

In this study the yeast cells were only a model for the abstract mathematical approach because diffusion, active transport and endocytosis are equally responsible for the establishment and maintenance of cortical polarity in simple organisms, plants and higher animals.

"We therefore assume that our results may be almost universally valid," says Wedlich-Soldner. "And our approach provides an important step towards a spatially and temporally quantifiable model of the cell."

Citation: Eugenio Marco, Roland Wedlich-Söldner, Rong Li, Steven J. Altschuler und Lani F. Wu, Endocytosis Optimizes the Dynamic Localization of Membrane Proteins that Regulate Cortical Polarity, Cell, 20. April 2007

Source: Max-Planck-Gesellschaft

Explore further: How proteins evolved the capacity for movement within cells

Related Stories

Quantum Criticality in life's proteins (Update)

Apr 15, 2015

(—Stuart Kauffman, from the University of Calgary, and several of his colleagues have recently published a paper on the Arxiv server titled 'Quantum Criticality at the Origins of Life'. The id ...

Light replaces the needle

Jan 21, 2015

One in twelve children are born prematurely in Switzerland. If hypoglycemia develops in these premature babies and persists for over an hour, it can affect brain development. In order to prevent this, the ...

Architecture of a lipid transport protein revealed

Nov 13, 2014

For the first time, the complex architecture of a protein that controls the transport of lipids between the two layers of a cell membrane has been described. With this structure, Biochemists from the University ...

Recommended for you

How proteins evolved the capacity for movement within cells

13 hours ago

The process behind how the molecular components of living organisms start to move has been explained for the first time in new research published by Science and it is an intricate set of dance steps where the tempo is set ...

How do neural cells respond to ischemia?

14 hours ago

A group of researchers from the Lomonosov Moscow State University, in collaboration with their Irish colleagues from the University College Cork, has studied the early response of cells to ischemia, which ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.