The Arp2/3 complex is essential for the actin-based motility of Listeria monocytogenes.
Actin polymerisation is thought to drive the movement of eukaryotic cells and some intracellular pathogens such as Listeria monocytogenes. The Listeria surface protein ActA synergises with recruited host proteins to induce actin polymerisation, propelling the bacterium through the host cytoplasm [1]. The Arp2/3 complex is one recruited host factor [2] [3]; it is also believed to regulate actin dynamics in lamellipodia [4] [5]. The Arp2/3 complex promotes actin filament nucleation in vitro, which is further enhanced by ActA [6] [7]. The Arp2/3 complex also interacts with members of the Wiskott-Aldrich syndrome protein (WASP) [8] family - Scar1 [9] [10] and WASP itself [11]. We interfered with the targeting of the Arp2/3 complex to Listeria by using carboxy-terminal fragments of Scar1 that bind the Arp2/3 complex [11]. These fragments completely blocked actin tail formation and motility of Listeria, both in mouse brain extract and in Ptk2 cells overexpressing Scar1 constructs. In both systems, Listeria could initiate actin cloud formation, but tail formation was blocked. Full motility in vitro was restored by adding purified Arp2/3 complex. We conclude that the Arp2/3 complex is a host-cell factor essential for the actin-based motility of L. monocytogenes, suggesting that it plays a pivotal role in regulating the actin cytoskeleton.
May
R C
RC
Department of Biochemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Hall
M E
ME
Higgs
H N
HN
Pollard
T D
TD
Chakraborty
T
T
Wehland
J
J
Machesky
L M
LM
Sechi
A S
AS
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001921:Brain / Q000382:microbiology; D002465:Cell Movement; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008089:Listeria monocytogenes / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D051316:Wiskott-Aldrich Syndrome Protein; D051300:Wiskott-Aldrich Syndrome Protein Family
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; C495927:Actr2 protein, mouse; C495929:Actr3 protein, mouse; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011506:Proteins; C495768:Was protein, mouse; C495774:Wasf1 protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D051300:Wiskott-Aldrich Syndrome Protein Family; C072980:actA protein, Listeria monocytogenes