Trends in Microbiology
Research updateCollective efforts to modulate the host actin cytoskeleton by Salmonella type III-secreted effector proteins
Section snippets
Signal interceptors: SopB and SopE command the signal transduction pathways
Salmonella entry into host cells is accompanied by extensive rearrangements of the host cell actin cytoskeleton7, 8. These rearrangements and the subsequent entry of Salmonella are abolished when actin polymerization is inhibited by cytochalasins9. Although many Salmonella genes are required for the induction of such rearrangements, the details of how this reorganization occurs are only now beginning to come to light.
The actin cytoskeleton plays a pivotal role in many cellular processes,
Front-line fighters: SipA and SipC modulate host actin dynamics
The discovery that SipA binds actin was the first indication that Salmonella can modulate host actin dynamics directly and established that, in addition to the effectors that activate the signal transduction pathways involved in actin cytoskeleton rearrangements, Salmonella also dispatches actin-binding proteins into host cells.
In the search for SipA-interacting host proteins, T-plastin (fimbrin) was originally found to form a complex with SipA (Ref. 12); however, no evidence for direct binding
Working together: bacterial and host actin-modulating proteins
One of the most exciting discoveries about actin polymerization is the role of the Arp2/3 complex and its regulation. It illustrates perfectly how signal transduction pathways are tightly coupled with actin-binding proteins to regulate actin dynamics in response to external stimuli. The purified Arp2/3 complex alone can nucleate the formation of actin filaments15. This activity is greatly increased by signaling molecules, such as N-WASP, that mediate the interaction between Cdc42 and the Arp2/3
Challenges ahead
Tremendous progress has been made in understanding the molecular mechanisms of Salmonella-induced actin cytoskeleton rearrangements during the past few years. This exciting field is poised to advance even further as we identify the functions of more type III effectors. It will be extremely interesting to see how they exert their unique functions in a cooperative environment containing not only the effectors themselves but also the vast array of host actin-binding proteins. Furthermore, although
References (22)
Salmonella typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells
Cell
(1998)Contact with epithelial cells induces the formation of surface appendages on Salmonella typhimurium
Cell
(1994)The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly
Cell
(1999)Requirement of CDC42 for Salmonella-induced cytoskeletal and nuclear responses
Science
(1996)Identification of SopE2 from Salmonella typhimurium, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell
Mol. Microbiol.
(2000)Identification of SopE2, a Salmonella secreted protein which is highly homologous to SopE and involved in bacterial invasion of epithelial cells
J. Bacteriol.
(2000)Role of the S. typhimurium actin-binding protein SipA in bacterial internalization
Science
(1999)- et al.
Direct nucleation and bundling of actin by the SipC protein of invasive Salmonella
EMBO J.
(1999) Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria
Nature
(1993)Cytoskeletal rearrangements accompanying Salmonella entry into epithelial cells
J. Cell Sci.
(1991)
Striking a balance: modulation of the actin cytoskeleton by Salmonella
Proc. Natl. Acad. Sci. U. S. A.
Cited by (15)
Exploitation of Host Signal Transduction Pathways Induced by Streptococcus pneumoniae
2015, Streptococcus Pneumoniae: Molecular Mechanisms of Host-Pathogen InteractionsThe functional interface between Salmonella and its host cell: Opportunities for therapeutic intervention
2005, Trends in Pharmacological SciencesBacteria-host-cell interactions at the plasma membrane: Stories on actin cytoskeleton subversion
2005, Developmental CellCitation Excerpt :Finally, Rac/Cdc42 can interact with additional effectors implicated in actin dynamics and turnover, for instance, p65PAK driving LIM kinase-mediated ADF/cofilin inactivation (Raftopoulou and Hall, 2004). Hence, as observed with other motility processes (Disanza et al., 2005; Loisel et al., 1999), a concerted action of both actin filament nucleators and depolymerizing factors (such as ADF/cofilin) during the different stages of Salmonella entry may be required to allow for efficient invasion (Dai et al., 2004; Zhou, 2001). Together, the exact contributions to Sop-mediated entry of Cdc42 versus Rac activity and of their common as well as distinct downstream actin regulators will require more detailed analyses, certainly including knockout or knockdown approaches in the host.
Manipulation of the host actin cytoskeleton by Salmonella - All in the name of entry
2005, Current Opinion in MicrobiologyStructure-function analysis of invasion plasmid antigen C (IpaC) from Shigella flexneri
2003, Journal of Biological ChemistryCitation Excerpt :As with Salmonella, the role of actin nucleation in invasion by S. flexneri is not immediately obvious. It is possible that IpaC-mediated actin nucleation: 1) contributes to the localization of actin polymerization in host cells (34, 35) or 2) permits the quick burst of actin polymerization needed for rapid entry. It is also possible that actin nucleation by IpaC has a more direct role inShigella invasion.