title: S100A7 (psoriasin) interacts with epidermal fatty acid binding protein and localizes in focal adhesion-like structures in cultured keratinocytes.
abstract: S100 proteins are calcium-responsive signaling proteins that are overexpressed in cancer and inflammatory diseases. They act by forming complexes with target proteins to modify target protein function. Identifying S100 intracellular distribution, site of action, and protein targets are important goals. S100A7 (psoriasin) is an important member of this family that is markedly overexpressed in psoriatic keratinocytes; however, its role in disease progression is poorly understood. In this study, we express S100A7 in normal keratinocytes as a means to study S100A7 function. We show that S100A7 is present in the cytosol and in BiP/GRP78-positive (endoplasmic reticulum) tubular structures. When cells are challenged with elevated intracellular calcium, cytoplasmic S100A7 redistributes to alpha-actinin- and paxillin-positive peripheral structures that contact the substrate surface. Epidermal fatty acid binding protein is also overexpressed in psoriasis, and is a putative target of S100A7 in keratinocytes. To study this interaction, we coexpressed S100A7 and epidermal fatty acid binding protein. These studies indicate that S100A7 and epidermal fatty acid binding protein colocalize in the cytoplasm in untreated cultures, and localize in peripheral structures in response to calcium challenge. In addition, S100A7 expression appears to stabilize epidermal fatty acid binding protein level, and vice versa. Moreover, the proteins can be coprecipitated in the presence of bifunctional cross-linker, suggesting that they are part of a common complex. The colocalization with alpha-actinin and paxillin suggests that S100A7 and epidermal fatty acid binding protein colocalize in focal adhesion-like structures following calcium treatment.
authors.affiliation: Department of Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Ruse
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Broome
authors.forename: Richard L
authors.initials: RL
authors.lastname: Eckert
mesh_terms: D000185:Actinin / Q000032:analysis; D015415:Biomarkers; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000032:analysis; D000091342:Endoplasmic Reticulum Chaperone BiP; D004817:Epidermis / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D022001:Focal Adhesions / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D009363:Neoplasm Proteins; D051419:Paxillin; D010750:Phosphoproteins / Q000032:analysis; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D025521:Tumor Suppressor Proteins
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; C000717247:HSPA5 protein, human; D009363:Neoplasm Proteins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D025521:Tumor Suppressor Proteins; D000185:Actinin; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium