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Stabilisation for branched actin networks supports cells on the move

The molecular machinery in our bodies is complex and needs to be tightly regulated. Without this regulation, one of the core elements of this machinery, the actin cytoskeleton, can cause disruption and damage, as happens with metatastic cancers. Recent work from the research team of Professor Carolyn Moores has now uncovered how cortactin stabilises these actin branches.

Cortactin (bright green) bridges the components of the actin branching complex (orange, red, yellow, green, cyan, blue, purple) to stabilize the connection to the actin branch (white). [Image: Professor Moores' lab]

As solid as our bodies may seem, the cells from which they are built are often on the move, dynamically responding to our environment, metabolism and health. This teeming activity is visible at the microscopic level, for example as immune cells patrol for incursions by infectious agents or as wounds close and heal.

The molecular machinery that drives cell movement is complex and must be tightly regulated. One of the core elements of that machinery is the actin cytoskeleton, a dynamic network of filaments built from the protein actin that is found everywhere in our cells. When regulation of the actin cytoskeleton is lost, cells can wander to unsuitable places, with the potential to cause disruption and damage, as happens in metastatic cancers.

An important feature of the actin motility machinery is its ability to form branched filament networks that push at the front of a moving cell to drive it forward. The protein cortactin has been known for some time to be an important regulator of actin branches, but how it performs this important function was not understood.

Recent work from the research team of Professor Carolyn Moores has now uncovered how cortactin stabilises these actin branches. Branched actin networks in the presence of cortactin were mixed in a test tube and images were collected using a powerful electron microscope. Computational analysis of the data allowed the branched actin filaments to be visualised in three dimensions and revealed how cortactin binds across the actin branches to stabilise them.

Professor Moores commented: "We discovered that cortactin works in a completely different way to what was originally proposed. By showing what cortactin looks like at actin branches, we now understand how it stabilises them, and how that stabilisation could be controlled. Our result demonstrates the remarkable power of structural biology in visualising the molecules that allow our cells to work properly." Future work, both in test tubes and in cells, will aim to understand how cortactin cooperates or competes with other actin regulators.

This work was part of the European-funded collaborative project ArpComplexity held jointly by the Moores group at Birkbeck together with Michael Way's lab at the Francis Crick Institute, London, and Edgar Gomes' group at the Institute of Molecular Medicine, Lisbon, Portugal.

Further Information

Cortactin stabilizes actin branches by bridging activated Arp2/3 to its nucleated actin filament - read more about this research.

Find out more about research and study in the School of Natural Sciences.

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