title: Dictyostelium discoideum nucleoside diphosphate kinase C plays a negative regulatory role in phagocytosis, macropinocytosis and exocytosis.
abstract: Nucleoside diphosphate kinases (NDPKs) are ubiquitous phosphotransfer enzymes responsible for producing most of the nucleoside triphosphates except for ATP. This role is important for the synthesis of nucleic acids and proteins and the metabolism of sugars and lipids. Apart from this housekeeping role NDPKs have been shown to have many regulatory functions in diverse cellular processes including proliferation and endocytosis. Although the protein has been shown to have a positive regulatory role in clathrin- and dynamin-mediated micropinocytosis, its roles in macropinocytosis and phagocytosis have not been studied. The additional non-housekeeping roles of NDPK are often independent of enzyme activity but dependent on the expression level of the protein. In this study we altered the expression level of NDPK in the model eukaryotic organism Dictyostelium discoideum through antisense inhibition and overexpression. We demonstrate that NDPK levels affect growth, endocytosis and exocytosis. In particular we find that Dictyostelium NDPK negatively regulates endocytosis in contrast to the positive regulatory role identified in higher eukaryotes. This can be explained by the differences in types of endocytosis that have been studied in the different systems - phagocytosis and macropinocytosis in Dictyostelium compared with micropinocytosis in mammalian cells. This is the first report of a role for NDPK in regulating macropinocytosis and phagocytosis, the former being the major fluid phase uptake mechanism for macrophages, dendritic cells and other (non dendritic) cells exposed to growth factors.
authors: Department of Microbology, La Trobe University, Victoria, Australia.
authors: Sarah J
authors: SJ
authors: Annesley
authors: Ruzica
authors: R
authors: Bago
authors: Maja Herak
authors: MH
authors: Bosnar
authors: Vedrana
authors: V
authors: Filic
authors: Maja
authors: M
authors: Marinović
authors: Igor
authors: I
authors: Weber
authors: Anil
authors: A
authors: Mehta
authors: Paul R
authors: PR
authors: Fisher
mesh_terms: D000199:Actins / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D004023:Dictyostelium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D005089:Exocytosis / Q000187:drug effects; D016982:Micrococcus luteus / Q000187:drug effects; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D010873:Pinocytosis / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors; D014170:Transformation, Genetic / Q000187:drug effects
chemical_list: D000199:Actins; D002147:Calmodulin; D003470:Culture Media; D054778:NM23 Nucleoside Diphosphate Kinases