Hierarchical Phosphorylation of Apical Membrane Antigen 1 is Required for Efficient Red Blood Cell Invasion by Malaria Parasites

Overview

Journal Sci Rep

Specialty Science

Date 2016 Oct 5

PMID 27698395

Citations 17

Authors

Boris Prinz

Katherine L Harvey

Louisa Wilcke

Ulrike Ruch

Klemens Engelberg

Laura Biller

Isabelle Lucet

Steffen Erkelenz

Dorothee Heincke

Tobias Spielmann

Christian Doerig

Conrad Kunick

Brendan S Crabb

Paul R Gilson

Tim W Gilberger

Affiliations

Soon will be listed here.

Abstract

Central to the pathogenesis of malaria is the proliferation of Plasmodium falciparum parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated sequence of receptor-ligand interactions between the parasite and host cell. One key ligand, Apical Membrane Antigen 1 (AMA1), is a leading blood-stage vaccine and previous work indicates that phosphorylation of its cytoplasmic domain (CPD) is important to its function during invasion. Here we investigate the significance of each of the six available phospho-sites in the CPD. We confirm that the cyclic AMP/protein kinase A (PKA) signalling pathway elicits a phospho-priming step upon serine 610 (S), which enables subsequent phosphorylation in vitro of a conserved, downstream threonine residue (T) by glycogen synthase kinase 3 (GSK3). Both phosphorylation steps are required for AMA1 to function efficiently during invasion. This provides the first evidence that the functions of key invasion ligands of the malaria parasite are regulated by sequential phosphorylation steps.

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