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Dictyostelim discoideum nucleoside diphosphate kinase C plays a negative regulatory role in phagocytosis, macropinocytosis and exocytosis

Annesley, Sarah J.; Bago, Ružica; Herak Bosnar, Maja; Filić, Vedrana; Marinović, Maja; Weber, Igor; Mehta, Anil; Fisher, Paul R. (2011) Dictyostelim discoideum nucleoside diphosphate kinase C plays a negative regulatory role in phagocytosis, macropinocytosis and exocytosis. PLoS Biology, 6 (10). e26024/1-e26024/11. ISSN 1544-9173

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Abstract

Background information 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 diverse functions such as roles in proliferation and endocytosis. These additional roles are independent of enzyme activity but often are dependent on the expression level of the protein. Results In this study we altered the expression level of NDPK in the model eukaryotic organism Dictyostelium discoideum and demonstrated that NDPK plays a role in growth, endocytosis and exocytosis. In Dictyostelium NDPK negatively regulates endocytosis in contrast to the positive regulatory role identified in higher eukaryotes and this may 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. The biological functions identified in these experiments are consistent with NDPK’s function as a metastatic suppressor and suggest that the metastatic suppressor roles may have evolved from an ancestral eukaryotic function in growth and endocytic vesicle trafficking. Conclusions NDPK in the model eukaryote Dictyostelium discoideum plays a role in growth, exocytosis and endocytosis. This is the first report of NDPK negatively regulating macropinocytosis which is the major fluid phase uptake mechanism for macrophage and dendritic cells and non dendritic cells exposed to growth factors.

Item Type: Article
Uncontrolled Keywords: NDKC; Dictyostelium discoideum; phagocytosis; macropinocytosis; exocytosis
Subjects: NATURAL SCIENCES > Biology
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Projects:
Project titleProject leaderProject codeProject type
Molekularne interakcije u diferencijaciji limfocita[113165] Mariastefania Antica098-0982913-2332MZOS
Povećanje transdukcije adenovirusnih vektora i otpornost stanica na citostatike[173311] Andreja Ambriović Ristov098-0982913-2850MZOS
Uloga gena nm23 u karcinomu pločastog epitela usne šupljine[202030] Maja Herak-Bosnar098-0982464-2513MZOS
Depositing User: Ružica Bago
Date Deposited: 06 Jul 2015 10:17
Last Modified: 06 Jul 2015 10:17
URI: http://fulir.irb.hr/id/eprint/2016
DOI: 10.1371/journal.pone.0026024

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