title: SipC multimerization promotes actin nucleation and contributes to Salmonella-induced inflammation.
abstract: Actin nucleation is the rate-limiting step in actin assembly and is regulated by actin-binding proteins and signal transduction molecules. Salmonella enterica serovar Typhimurium exploits actin dynamics by reorganizing the host actin cytoskeleton to facilitate its own uptake. SipC is a Salmonella actin-binding protein that nucleates actin filament formation in vitro. The molecular mechanism by which SipC nucleates actin is not known. We show here that SipC(199-409) forms multimers to promote actin nucleation. We found that wild-type SipC(199-409) forms dimers and multimers while SipC(199-409)#1, a nucleation mutant, is less efficient in dimer and multimer formation. Biochemical analysis suggested that SipC(199-409) might form parallel dimers in an extended conformation. Furthermore, a mutant Salmonella strain that was defective in forming the SipC multimer and deficient in actin nucleation failed to cause severe colitis in a mouse model. These results allow us to present a model in which SipC forms multimers to promote actin nucleation.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: JiHoon
authors.initials: J
authors.lastname: Chang
authors.forename: Sebenzile K
authors.initials: SK
authors.lastname: Myeni
authors.forename: Tsang Long
authors.initials: TL
authors.lastname: Lin
authors.forename: Ching Ching
authors.initials: CC
authors.lastname: Wu
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Staiger
authors.forename: Daoguo
authors.initials: D
authors.lastname: Zhou
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002850:Chromatography, Gel; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D016133:Polymerase Chain Reaction; D012475:Salmonella / Q000378:metabolism* / Q000472:pathogenicity; D012480:Salmonella Infections / Q000382:microbiology
chemical_list: D000199:Actins; D001426:Bacterial Proteins; C094578:Salmonella invasion protein C