Conditional degradation of plasmodium calcineurin reveals functions in parasite colonization of both host and vector

Philip, N. and Waters, A. P. (2015) Conditional degradation of plasmodium calcineurin reveals functions in parasite colonization of both host and vector. Cell Host and Microbe, 18(1), pp. 122-131. (doi: 10.1016/j.chom.2015.05.018) (PMID:26118994) (PMCID:PMC4509507)

Abstract

Functional analysis of essential genes in the malarial parasite, Plasmodium, is hindered by lack of efficient strategies for conditional protein regulation. We report the development of a rapid, specific, and inducible chemical-genetic tool in the rodent malaria parasite, P. berghei, in which endogenous proteins engineered to contain the auxin-inducible degron (AID) are selectively degraded upon adding auxin. Application of AID to the calcium-regulated protein phosphatase, calcineurin, revealed functions in host and vector stages of parasite development. Whereas depletion of calcineurin in late-stage schizonts demonstrated its critical role in erythrocyte attachment and invasion in vivo, stage-specific depletion uncovered roles in gamete development, fertilization, and ookinete-to-oocyst and sporozoite-to-liver stage transitions. Furthermore, AID technology facilitated concurrent generation and phenotyping of transgenic lines, allowing multiple lines to be assessed simultaneously with significant reductions in animal use. This study highlights the broad applicability of AID for functional analysis of proteins across the Plasmodium life cycle.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Philip, Dr Nisha and Waters, Professor Andy
• Authors: Philip, N., and Waters, A. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Cell Host and Microbe
• Publisher: Cell Press
• ISSN: 1931-3128
• ISSN (Online): 1934-6069
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Cell Host and Microbe 18(1):122-131
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
46686	1	Conditional translational repression: a core regulatory mechanism of gene expression during development of the malaria parasite.	Andrew Waters	Wellcome Trust (WELLCOME)	083811/Z/07/Z	III - PARASITOLOGY