title: Association of small Rho GTPases and actin ring formation in epithelial cells during the invasion by Candida albicans.
abstract: Invasion of epithelial cells is a major virulence determinant of Candida albicans; however, the molecular events that occur during invasion are not discerned. This study is aimed to elucidate the role of the host's actin remodeling and involvement of small GTPases during invasion. Actin filaments formed a rigid ring-like structure in the rabbit corneal epithelial cell line SIRC after C. albicans invasion. During invasion, an increase in the mRNA content of Cdc42, Rac1 and RhoA GTPase was observed in SIRC cells. Immunochemical staining and expression of chimeric green fluorescent protein (GFP)-GTPases showed that all three GTPases colocalize at invasion and actin polymerization sites. This colocalization was not seen in SIRC cells expressing a GFP-tagged dominant-negative mutant of GTPases. Inhibition of invasion was observed in SIRC cells expressing dominant-negative mutants of Rac1 and RhoA GTPases. Involvement of zonula occludens-1 (ZO-1) was observed in the process of actin-mediated endocytosis of C. albicans. Actin, GTPases and ZO-1 were colocalized in epithelial cells during uptake of polymethylmethacrylate beads coated with spent medium from a C. albicans culture. The results indicate that host actin remodeling and recruitment of small GTPases occur during invasion and molecules that are shed or secreted by C. albicans are probably responsible for cytoskeletal reorganization.
authors.affiliation: National Centre for Cell Science, University of Pune Campus, Pune, India.
authors.forename: Ashwini N
authors.initials: AN
authors.lastname: Atre
authors.forename: Sachin V
authors.initials: SV
authors.lastname: Surve
authors.forename: Yogesh S
authors.initials: YS
authors.lastname: Shouche
authors.forename: Jomon
authors.initials: J
authors.lastname: Joseph
authors.forename: Milind S
authors.initials: MS
authors.lastname: Patole
authors.forename: Rajendra L
authors.initials: RL
authors.lastname: Deopurkar
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002176:Candida albicans / Q000502:physiology*; D002460:Cell Line; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology*; D020869:Gene Expression Profiling; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D062826:Zonula Occludens-1 Protein; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D062826:Zonula Occludens-1 Protein; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein