Synthesis and secretion of proteins by released malarial parasites.
Controlled mechanical homogenization of Plasmodium falciparum-infected erythrocytes releases parasites of a quality sufficient for studying the export of newly synthesized plasmodial proteins. Protein synthesis occurs within intact released parasites as defined by resistance of acid-insoluble incorporation of radiolabel to high levels of exogenously added EDTA, hexokinase, and RNaseA. While exogenously added ATP and erythrocyte cytosol were not essential for biosynthetic activity at levels comparable to that seen in infected erythrocytes, the addition of an extracellular ATP regenerating system (ARS) stimulated the synthesis of parasite proteins. Conversely, parasite viability and biosynthetic activity are decreased by the addition of a non-hydrolyzable ATP analogue (ATP gamma S), ADP, or ATP in the absence of a regenerating system. These data suggest a metabolic interdependence between extracellular energy metabolism and biosynthetic functions within the parasite. The export of a predominant subset of proteins was retarded in the presence of Brefeldin A, indicating the existence of a classical secretory pathway characteristic of that seen in higher eukaryotic cells. Interestingly, a Brefeldin A-insensitive component of export was also consistently observed; this may suggest the existence of an additional alternative secretory mechanism in malaria.
Elmendorf
H G
HG
Department of Microbiology and Immunology, Stanford University School of Medicine, CA.
Bangs
J D
JD
Haldar
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020126:Brefeldin A; D003517:Cyclopentanes / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D006593:Hexokinase / Q000378:metabolism; D008854:Microscopy, Electron; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism
D000900:Anti-Bacterial Agents; D003517:Cyclopentanes; D015800:Protozoan Proteins; D020126:Brefeldin A; D000255:Adenosine Triphosphate; D006593:Hexokinase; D012259:Ribonuclease, Pancreatic