Synthetic polyamines promote rapid lamellipodial growth by regulating actin dynamics

Iliana Nedeva, Girish Koripelly, David Caballero, Lionel Chièze, Bérangère Guichard, Benoît Romain, Erwan Pencreach, Jean-Marie Lehn, Marie-France Carlier and Daniel Riveline ()
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Iliana Nedeva: Laboratory of Cell Physics, ISIS/IGBMC, Université de Strasbourg and CNRS (UMR 7006)
Girish Koripelly: Laboratoire de Chimie Supramoléculaire, ISIS, Université de Strasbourg and CNRS (UMR 7006)
David Caballero: Laboratory of Cell Physics, ISIS/IGBMC, Université de Strasbourg and CNRS (UMR 7006)
Lionel Chièze: Dynamique du Cytosquelette, Laboratoire d'Enzymologie et Biochimie Structurales UPR A9063 CNRS
Bérangère Guichard: Dynamique du Cytosquelette, Laboratoire d'Enzymologie et Biochimie Structurales UPR A9063 CNRS
Benoît Romain: Service de Chirurgie Générale et Digestive, Hôpitaux Universitaires de Strasbourg
Erwan Pencreach: EA3430, Université de Strasbourg, Faculté de Médecine
Jean-Marie Lehn: Laboratoire de Chimie Supramoléculaire, ISIS, Université de Strasbourg and CNRS (UMR 7006)
Marie-France Carlier: Dynamique du Cytosquelette, Laboratoire d'Enzymologie et Biochimie Structurales UPR A9063 CNRS
Daniel Riveline: Laboratory of Cell Physics, ISIS/IGBMC, Université de Strasbourg and CNRS (UMR 7006)

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract Cellular protrusions involved in motile processes are driven by site-directed assembly of actin filaments in response to Rho-GTPase signalling. So far, only chemical compounds depolymerizing actin or stabilizing filaments, inhibiting N-WASP, Arp2/3 or formins, have been used to eliminate the formation of protrusions, while Rho-GTPase-dominant positive strategies have been designed to stimulate protrusions. Here we describe the design of four polyamines (macrocyclic and branched acyclic), and show that they enter the cell and induce specific growth of actin-enriched lamellipodia within minutes. The largest increase in cell area is obtained with micromolar amounts of a branched polyamine harbouring an 8-carbon chain. These polyamines specifically target actin both in vitro and in vivo. Analysis of their effects on filament assembly dynamics and its regulation indicates that the polyamines act by slowing down filament dynamics and by enhancing actin nucleation. These compounds provide new opportunities to study the actin cytoskeleton in motile and morphogenetic processes.

Date: 2013
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DOI: 10.1038/ncomms3165

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