TY - JOUR
T1 - Bacterial nucleators
T2 - actin' on actin
AU - Bugalhão, Joana N.
AU - Mota, Luis Jaime
AU - Saraiva Franco, Irina
N1 - Sem PDF conforme Despacho.
Work in the laboratory of IF has been funded by grants PTDC/BIA-MIC/2821/2012 from Fundacao para a Ciencia e Tecnologia (FCT) and PCOFUND-GA-2009-246542 from the European Union Seventh Framework Programme FP7/2007-2013 (to IF) and UID/Multi/04378/2013 from FCT (to UCIBIO).
PY - 2015/12
Y1 - 2015/12
N2 - The actin cytoskeleton is a key target of numerous microbial pathogens, including protozoa, fungi, bacteria and viruses. In particular, bacterial pathogens produce and deliver virulence effector proteins that hijack actin dynamics to enable bacterial invasion of host cells, allow movement within the host cytosol, facilitate intercellular spread or block phagocytosis. Many of these effector proteins directly or indirectly target the major eukaryotic actin nucleator, the Arp2/3 complex, by either mimicking nucleation promoting factors or activating upstream small GTPases. In contrast, this review is focused on a recently identified class of effector proteins from Gram-negative bacteria that function as direct actin nucleators. These effector proteins mimic functional activities of formins, WH2-nucleators and Ena/VASP assembly promoting factors demonstrating that bacteria have coopted the complete set of eukaryotic actin assembly pathways. Structural and functional analyses of these nucleators have revealed several motifs and/or mechanistic activities that are shared with eukaryotic actin nucleators. However, functional effects of these proteins during infection extend beyond plain actin polymerization leading to interference with other host cell functions such as vesicle trafficking, cell cycle progression and cell death. Therefore, their use as model systems could not only help in the understanding of the mechanistic details of actin polymerization but also provide novel insights into the connection between actin dynamics and other cellular pathways.
AB - The actin cytoskeleton is a key target of numerous microbial pathogens, including protozoa, fungi, bacteria and viruses. In particular, bacterial pathogens produce and deliver virulence effector proteins that hijack actin dynamics to enable bacterial invasion of host cells, allow movement within the host cytosol, facilitate intercellular spread or block phagocytosis. Many of these effector proteins directly or indirectly target the major eukaryotic actin nucleator, the Arp2/3 complex, by either mimicking nucleation promoting factors or activating upstream small GTPases. In contrast, this review is focused on a recently identified class of effector proteins from Gram-negative bacteria that function as direct actin nucleators. These effector proteins mimic functional activities of formins, WH2-nucleators and Ena/VASP assembly promoting factors demonstrating that bacteria have coopted the complete set of eukaryotic actin assembly pathways. Structural and functional analyses of these nucleators have revealed several motifs and/or mechanistic activities that are shared with eukaryotic actin nucleators. However, functional effects of these proteins during infection extend beyond plain actin polymerization leading to interference with other host cell functions such as vesicle trafficking, cell cycle progression and cell death. Therefore, their use as model systems could not only help in the understanding of the mechanistic details of actin polymerization but also provide novel insights into the connection between actin dynamics and other cellular pathways.
KW - actin
KW - nucleation
KW - bacterial virulence
KW - effector protein
KW - secretion system
KW - CHLAMYDIA-TRACHOMATIS TARP
KW - III SECRETION SYSTEM
KW - BURKHOLDERIA-PSEUDOMALLEI
KW - ARP2/3 COMPLEX
KW - FILAMENT NUCLEATION
KW - EFFECTOR VOPL
KW - LISTERIA-MONOCYTOGENES
KW - LEGIONELLA-PNEUMOPHILA
KW - RICKETTSIA-RICKETTSII
KW - INVASIVE SALMONELLA
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85013858446&origin=resultslist&sort=plf-f&src=s&st1
U2 - 10.1093/femspd/ftv078
DO - 10.1093/femspd/ftv078
M3 - Review article
C2 - 26416078
SN - 2049-632X
VL - 73
JO - Pathogens and Disease
JF - Pathogens and Disease
IS - 9
M1 - ftv078
ER -