Research groups at the University of Helsinki and the Jacques Monod Institut, Paris, have discovered a new molecular mechanism that drives cell migration. The discovery elucidates the mechanisms driving the uncontrolled migration of cancer cells and also modifies the ‘documentary view’ of cell migration.

The mobility of cells in our bodies is important for wound healing, as well as for immune cells to patrol our tissues to hunt for bacterial and viral pathogens. cause. On the other hand, uncontrolled cell migration is a marker of cancer invasion and metastasis.

The machinery that drives cell movement is a complex network of dynamic fibers composed of an actin protein. Actin exists as monomers, but like Lego bricks, different types of filamentous structures can be built from actin monomers in the cell. The actin filaments are organized in the cell in such a way that their rapidly elongated anode ends face the plasma membrane, while their cathode ends point away from the plasma membrane. The elongation of the actin filaments at their anode terminals relative to the plasma membrane exerts a force that pushes the cell edge forward during cell migration. To maintain a sufficient supply of monomeric actin subunits for filament elongation, actin filaments must be rapidly disassembled within the cell, and this is thought to occur at their cathode terminals. An important factor limiting the detachment of actin filaments at their cathode ends is the Capping Protein, which binds very tightly to the anode ends of the filament to prevent elongation and shortening of the filament.

A new study published in Nature Cell Biology suggests the ‘documented view’ of cell migration needs to be revised. Research conducted principally by Academic Professor Pekka Lappalainen from HiLIFE Institute of Biotechnology, University of Helsinki, has revealed that a conserved actin-binding protein, Twinfilin, efficiently removes Capping Protein from the terminals fiber positive. This leads to demyelination of the filaments also from their ‘old’ anode terminals, which no longer push the edge of the cell forward. In the absence of Twinfilin, actin filament recycling is reduced, the filaments push the cell edge forward less efficiently, and cell migration is slower.

“Our results suggest that Twinfilin and Capping Protein play a role in creating a ‘molecular clock’ together, ensuring that the ‘producing’ actin filaments that push the plasma membrane have an adequate supply,” said Lappalainen. actin monomers, while the ‘aged’ actin filaments are no longer functionally disassembled.”

Dr. “This study highlights the need for several proteins with different functions to act in a synergistic manner to maintain normal morphology and function,” continued Markku Hakala, lead author of the study. of the actin network in the cell.”

Despite extensive studies, the exact mechanisms by which actin monomers are recycled in the cell remain elusive. New research adds an important piece to this puzzle by revealing how Capping Proteins are removed from the anode ends of actin filaments to allow them to be rapidly disassembled. These findings also form the basis for further studies to understand how abnormalities in actin detachment cause serious diseases and developmental disorders.

Lappalainen concludes: “Uncontrolled expression of Twinfilin is implicated in many diseases, such as breast cancer invasiveness and lymphoma progression. Thus, our work also elucidates the molecular mechanisms that drive uncontrolled cancer cell migration.”

Information sources:

Materials provided by University of Helsinki. Note: Content may have been modified in presentation and length.

References:

1. Twinfilin uncaps filament barbed ends to promote turnover of lamellipodial actin networks.

Markku Hakala, Hugo Wioland, Mari Tolonen, Tommi Kotila, Antoine Jegou, Guillaume Romet-Lemonne, Pekka Lappalainen. Nature Cell Biology, 2021;

DOI: https://www.nature.com/articles/s41556-020-00629-y

The article is translated and edited by ykhoa.org – please do not reup without permission!

Source: ScienceDaily

Link: https://www.sciencedaily.com/releases/2021/02/210209113840.htm

Author: Roxie Duong

Editing: Duong Ngoc