Actin-based motility of pathogens: the Arp2/3 complex is a central player. Microreview

Abstract

Bacterial actin‐based motility has provided cell biologists with tools that led to the recent discovery that, in many forms of actin‐based motilities, a key player is a protein complex named the Arp2/3 complex. The Arp2/3 complex is evolutionally conserved and made up of seven polypeptides involved in both actin filament nucleation and organization. Interestingly, this complex is inactive by itself and recent work has highlighted the fact that its activation is achieved differently in the different types of actin‐based motilities, including the well‐known examples of Listeria and Shigella motilities. Proteins of the WASP family and small G‐proteins are involved in most cases. It is interesting that bacteria bypass or mimic some of the events occurring in eukaryotic systems. The Shigella protein IcsA recruits N‐WASP and activates it in a Cdc42‐like fashion. This activation leads to Arp2/3 complex recruitment, activation of the complex and ultimately actin polymerization and movement. The Listeria ActA protein activates Arp2/3 directly and, thus, seems to mimic proteins of the WASP family. A breakthrough in the field is the recent reconstitution of the actin‐based motilities of Listeria and N‐WASP‐coated E. coli (IcsA) using a restricted number of purified cellular proteins including F‐actin, the Arp2/3 complex, actin depolymerizing factor (ADF or cofilin) and capping protein. The movement was more effective upon addition of profilin, α‐actinin and VASP (for Listeria). Bacterial actin‐based motility is now one of the best‐documented examples of the exploitation of mammalian cell machineries by bacterial pathogens.

Chlamydial TARP is a bacterial nucleator of actin

“…Bacteria such as Listeria, Shigella, Rickettsia, and Burkholderia, which replicate freely within the cytoplasm of the host cell, use an actin-based motility mechanism to spread directly from cell to cell (30)(31)(32)(33)(34)(35)(36)(37). This mechanism typically involves a bacterial outer membrane protein that recruits components of the host actin machinery, including the Arp2͞3 actin nucleation complex (38). Microbial pathogens also manipulate actin dynamics to promote, or avoid, internalization.…”

Détournement de fonctions cellulaires-clés par les bactéries pathogènes.

“…En effet, à l'instar des GEF cellulaires de la famille des protéines Dbl, les protéines SopE catalysent l'échange de GDP pour le GTP sur ces GTPases, ce qui conduit à une cascade d'activations aboutissant à la polymérisation de l'actine : les GTPases activées interagissent avec des protéines de la famille WASp, qui sont à leur tour activées et stimulent l'activité du complexe Arp2/3, nucléateur de l'actine [8]. En combinaison avec les protéines SopE, la protéine SipC, qui est insérée dans la membrane de la cellule, permettrait directement la nucléation des filaments d'actine [9].…”

“…Le comportement des EPEC ainsi que ceux des Yersinia ou d'Hélicobacter révèlent que les bactéries sont capables de moduler leur interaction avec les composants du cytosquelette dans un but autre que l'internalisation et qu'il en résulte une adhé-rence bien contrôlée. [8]. Cette polymérisation de l'actine a lieu à un pôle de la bactérie et lui fournit l'énergie nécessaire au mouvement, pouvant atteindre des vitesses de 10 µm par minute.…”

How the Study of Listeria Monocytogenes has Led to New Concepts in Biology

“…monocytogenes is not the only microorganism that exploits actin for intracellular movement. (for review, [57]). Shigella flexneri recruits on its surface, via the protein IscA, N-WASP which in turn activates Arp2/3 to mediate actin-based motility [58].…”