Scientists unravel the enigmatic mechanism behind actin branching – sciencedaily
The cells are characterized to be stable but very flexible. They constantly change their shape and even move through tissue. These vital properties are based on a dynamically organized network of branched actin filaments, which generates pushing forces to displace the cell membrane. An interdisciplinary team led by Peter Bieling and Stefan Raunser from the Max Planck Institute for Molecular Physiology (MPI) in Dortmund have now jointly revealed a previously unknown mechanism, explaining how the stopping of the growth of older actin filaments within the network promotes the formation of new. , thus maintaining the structure and function of the cytoskeleton, much like a good pruning of hedges in the garden.
Cells grow, divide, change shape, and move around. They structure the body and tissues, penetrate wounds to close them or drive out bacteria present in our blood. Cell mobility is a prerequisite for a variety of essential biological functions and is provided by the cytoskeleton. This dynamic protein network assembles inside the cell membrane and is responsible for the shape of the cell, its mechanical stability and its ability to move.
How tiny molecules fit together into large, powerful structures
A key part of the cytoskeleton is actin, which can self-assemble into filaments. But where does the pushing force of the cytoskeleton actually come from? The origin lies in a nucleation process that occurs just below the cell membrane. The nucleation of new actin filaments is initiated by a protein complex called Arp2 / 3, which is activated by membrane-bound nucleation-promoting factors (NPF). Apr2 / 3 forms the initial seed of a new filament and connects this seed to the side of the older filaments. After the initial formation of this actin seed, other actin monomers attach themselves and build a filament that grows against the membrane. This growth process generates the pushing force. The resulting structure of the actin network resembles a tree or a hedge, with many connected branches of actin filaments.
Pruning the actin hedge promotes the growth of new filaments
To ensure optimal transmission of power to the plasma membrane, the branched actin network requires continuous maintenance. A key player in this process is the styling protein. Its main task is to stop the elongation of the filaments before they get too long and to prevent the unproductive elongation of the filaments which move away from the cell membrane. Capping the actin filaments therefore has a similar effect to trimming a hedge: it keeps the (actin) hedge neat and tidy, much like a good pruning However, it also stimulates the production of budding ( actin branch) near the edges of the plant (membrane) through the Arp2 / 3 complex. The precise mechanism involved in how the capping protein controls the rate at which Arp2 / 3 forms new filaments was not previously understood.
How a molecular tentacle regulates branching
An interdisciplinary team of structural biologists and biochemists from MPI Dortmund, in collaboration with cell biologists from the University of Braunschweig, have now discovered the hitherto enigmatic mechanism behind the opposing function of the capping protein in the assembly of the branched network. A high-resolution structure of the styling protein linked to an actin filament end produced by co-first author Felipe Merino using electron cryomicroscopy revealed that the styling protein does much more than previously believed previously. It not only stops the growth of filaments, but also prevents the tip from interacting with other proteins. More importantly, it blocks the binding of nucleation-promoting factors (Arp2 / 3 activators) via a tiny “sprawling” extension. Johanna Funk, co-first author of the study, was able to show that the removal of this tentacle did not prevent the capping protein from stopping the growth of the filaments, but considerably inhibited the assembly of the network and the efficiency of the lamellipodial protrusion required for cell movement when working together. with all the other proteins needed to build branched networks.
“Studying the role of the styling protein from many different angles has uncovered details of how the core proteins that build branched actin networks do not act as separate actors as previously thought. , but truly as a functional unit. We hope that our findings will contribute to a better understanding of the cellular movement of healthy and diseased cells in the future, âsays Peter Bieling.
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