Calcium-dependent Phosphorylation of Serine Repeat Antigen 5 Triggers Merozoite Egress

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2018 May 3

PMID 29716996

Citations 11

Authors

Gayatri R Iyer

Shailja Singh

Inderjeet Kaur

Shalini Agarwal

Mansoor A Siddiqui

Abhisheka Bansal

Gautam Kumar

Ekta Saini

Gourab Paul

Asif Mohmmed

Chetan E Chitnis

Pawan Malhotra

Affiliations

Soon will be listed here.

Abstract

The human malaria parasite proliferates in red blood cells following repeated cycles of invasion, multiplication, and egress. serine repeat antigen 5 (PfSERA5), a putative serine protease, plays an important role in merozoite egress. However, regulation of its activity leading to merozoite egress is poorly understood. In this study, we show that PfSERA5 undergoes phosphorylation prior to merozoite egress. Immunoprecipitation of parasite lysates using anti-PfSERA5 serum followed by MS analysis identified calcium-dependent protein kinase 1 (PfCDPK1) as an interacting kinase. Association of PfSERA5 with PfCDPK1 was corroborated by co-sedimentation, co-immunoprecipitation, and co-immunolocalization analyses. Interestingly, PfCDPK1 phosphorylated PfSERA5 in the presence of Ca and enhanced its proteolytic activity. A PfCDPK1 inhibitor, purfalcamine, blocked the phosphorylation and activation of PfSERA5 both as well as in schizonts, which, in turn, blocked merozoite egress. Together, these results suggest that phosphorylation of PfSERA5 by PfCDPK1 following a rise in cytosolic Ca levels activates its proteolytic activity to trigger merozoite egress.

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