IDENTIFICATION AND LOCALIZATION OF ERD2 IN THE MALARIA PARASITE PLASMODIUM-FALCIPARUM - SEPARATION FROM SITES OF SPHINGOMYELIN SYNTHESIS AND IMPLICATIONS FOR ORGANIZATION OF THE GOLGI

The ERD2 gene product in mammalian cells and yeast is a receptor requi red for protein retention in the endoplasmic reticulum (ER); immunoloc alization studies indicate that the protein is concentrated in the cis Golgi. We have identified a homologue of ERD2 in the malaria parasite , Plasmodium falciparum (PfERD2). The deduced protein sequence is 42% identical to mammalian and yeast homologues and bears striking homolog y in its proposed tertiary structure. PfERD2 is tightly confined to a single focus of staining in the perinuclear region as seen by indirect immunofluorescence. This is redistributed by brefeldin A (BFA) to a d iffuse pattern similar to that of parasite BiP, a marker for the ER; r emoval of the drug results in recovery of the single focus, consistent with the localization of PfERD2 to the parasite Golgi and its partici pation in a retrograde transport pathway to the ER. Sphingomyelin synt hesis is a second resident activity of the cis Golgi whose organizatio n is sensitive to BFA in mammalian cells. Within the parasite it again localizes to a perinuclear region but does not reorganize upon BFA tr eatment. The results strongly suggest that these two activities are in distinct compartments of the Golgi in the malaria parasite.