New synthetic molecules target actin cytoskeleton
Ten minutes after addition of the compounds, an actin filamentous network grows; compare the outlined lamellipodia on the right panel and on the left panel.
Nat Commun July 29, 2013
July 29, 2013
The cytoskeleton, a major constituent of cells, is the target of numerous therapies. Its malfunction is involved in diseases such as cancer. Daniel Riveline’s team (Laboratory of Cell Physics, a joint team between ISIS (1) and IGBMC), together with Jean-Marie Lehn’s (1) and Marie-France Carlier’s (2) developed molecules that cause rapid growth of the lamellar networks of actin filaments, one of the three components of the cytoskeleton. Properties of these molecules, whose effects have been observed and decoded in vivo and in vitro, are novel. So far, only pharmacological agents destroying actin cytoskeleton were known. This study provides a new tool in pharmacology. The work is published in the Journal Nature Communications in its issue of 29 July 2013.
In contrast to what its name suggests, the cytoskeleton is a dynamic structure. Made of polymers in dynamic states, it is constantly under assembly, disassembly and renewal. Cytoskeleton affects many cellular processes such as cell movement, division or intracellular transport. Its malfunction can lead to diseases such as cancer. As a result, identification of new molecules that target the cytoskeleton is a major focus in basic and therapeutic research. Taxol®, for example, is an anticancer drug commonly used in chemotherapy, whose effect is to stabilize microtubules and thereby limiting the uncontrolled division of cancer cells.
Synthesized with supramolecular chemistry (3), the new compounds developed by the teams have unique properties: they cause in few minutes growth of actin lamellar networks inducing the formation of cell extensions called lamellipodia. Until now, synthetic molecules had the opposite effect, i.e. destroying actin cytoskeleton. While this process is continuously performed in cells, this is the first time that a pharmacological agent can induce growth of an actin network. The researchers have shown that action of these compounds is specific in vivo and they have identified the growth mechanisms of actin network by comparing in vivo and in vitro results.
These compounds are particularly interesting for research in molecular, cellular and developmental biology. This study is also a starting point for the design of new compounds inspired from supramolecular chemistry, with potential outcomes for new therapies targeting the cytoskeleton.
(1) Institut de Science et d’Ingénierie Supramoléculaires (CNRS/Université de Strasbourg)
(2) Laboratoire d'Enzymologie et Biochimie Structurales du CNRS
(3) Supramolecular chemistry can be defined as the chemistry of chemical entities resulting from the implementation of interactions between molecular objects, or the science of auto-assembly and auto-organization at the molecular level.