title: Calmodulin binding to Dfi1p promotes invasiveness of Candida albicans.
abstract: Candida albicans, a dimorphic fungus, undergoes hyphal development in response to many different environmental cues, including growth in contact with a semi-solid matrix. C. albicans forms hyphae that invade agar when cells are embedded in or grown on the surface of agar, and the integral membrane protein Dfi1p is required for this activity. In addition, Dfi1p is required for full activation of mitogen activated protein kinase Cek1p during growth on agar. In this study, we identified a putative calmodulin binding motif in the C-terminal tail of Dfi1p. This region of Dfi1p bound to calmodulin in vitro, and mutations that affected this region affected both calmodulin binding in vitro and invasive filamentation when incorporated into the full length Dfi1p protein. Moreover, increasing intracellular calcium levels led to calcium-dependent, Dfi1p-dependent Cek1p activation. We propose that conformational changes in Dfi1p in response to environmental conditions encountered during growth allow the protein to bind calmodulin and initiate a signaling cascade that activates Cek1p.
authors.affiliation: Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Talya R
authors.initials: TR
authors.lastname: Davis
authors.forename: Paola C
authors.initials: PC
authors.lastname: Zucchi
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kumamoto
mesh_terms: D000362:Agar; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D025301:Hyphae / Q000187:drug effects / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014774:Virulence / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D002147:Calmodulin; D005656:Fungal Proteins; D050505:Mutant Proteins; D000362:Agar; D002118:Calcium