Plasmodium falciparumprotein phosphatase PP7 is required for early ring-stage development

Abstract

AbstractWe previously reported that thePlasmodium falciparumputative serine/threonine protein phosphatase 7 (PP7) is a high confidence substrate of the cAMP-dependent protein kinase (PKA). Here we explore the function of PP7 in asexualP. falciparumblood stage parasites. We show that conditional disruption of PP7 leads to a severe growth arrest. We show that PP7 is a calcium-dependent phosphatase which interacts with calmodulin and calcium-dependent protein kinase 1 (CDPK1), consistent with a role in calcium signalling. Notably, PP7 was found to be dispensable for erythrocyte invasion, but was crucial for ring-stage development, with PP7-null parasites arresting shortly following invasion and showing no transition to ameboid forms. Phosphoproteomic analysis revealed that PP7 may regulate certain PKAc substrates. Its interaction with calmodulin and CDPK1 further emphasise a role in calcium signalling, while its impact on early ring development and PKAc substrate phosphorylation underscores its importance in parasite development.