Identification of an AP2-family protein that is critical for malaria liver stage development.

Liver-stage malaria parasites are a promising target for drugs and vaccines against malaria infection. However, little is currently known about gene regulation in this stage. In this study, we used the rodent malaria parasite Plasmodium berghei and showed that an AP2-family transcription factor, des...

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Main Authors: Shiroh Iwanaga, Izumi Kaneko, Tomomi Kato, Masao Yuda
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3492389?pdf=render
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spelling doaj-a6fb3e6d44d4493b864d0eb4faf3bfb62020-11-25T01:52:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4755710.1371/journal.pone.0047557Identification of an AP2-family protein that is critical for malaria liver stage development.Shiroh IwanagaIzumi KanekoTomomi KatoMasao YudaLiver-stage malaria parasites are a promising target for drugs and vaccines against malaria infection. However, little is currently known about gene regulation in this stage. In this study, we used the rodent malaria parasite Plasmodium berghei and showed that an AP2-family transcription factor, designated AP2-L, plays a critical role in the liver-stage development of the parasite. AP2-L-depleted parasites proliferated normally in blood and in mosquitoes. However, the ability of these parasites to infect the liver was approximately 10,000 times lower than that of wild-type parasites. In vitro assays showed that the sporozoites of these parasites invaded hepatocytes normally but that their development stopped in the middle of the liver schizont stage. Expression profiling using transgenic P. berghei showed that fluorescent protein-tagged AP2-L increased rapidly during the liver schizont stage but suddenly disappeared with the formation of the mature liver schizont. DNA microarray analysis showed that the expression of several genes, including those of parasitophorous vacuole membrane proteins, was significantly decreased in the early liver stage of AP2-L-depleted parasites. Investigation of the targets of this transcription factor should greatly promote the exploration of liver-stage antigens and the elucidation of the mechanisms of hepatocyte infection by malaria parasites.http://europepmc.org/articles/PMC3492389?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Shiroh Iwanaga
Izumi Kaneko
Tomomi Kato
Masao Yuda
spellingShingle Shiroh Iwanaga
Izumi Kaneko
Tomomi Kato
Masao Yuda
Identification of an AP2-family protein that is critical for malaria liver stage development.
PLoS ONE
author_facet Shiroh Iwanaga
Izumi Kaneko
Tomomi Kato
Masao Yuda
author_sort Shiroh Iwanaga
title Identification of an AP2-family protein that is critical for malaria liver stage development.
title_short Identification of an AP2-family protein that is critical for malaria liver stage development.
title_full Identification of an AP2-family protein that is critical for malaria liver stage development.
title_fullStr Identification of an AP2-family protein that is critical for malaria liver stage development.
title_full_unstemmed Identification of an AP2-family protein that is critical for malaria liver stage development.
title_sort identification of an ap2-family protein that is critical for malaria liver stage development.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description Liver-stage malaria parasites are a promising target for drugs and vaccines against malaria infection. However, little is currently known about gene regulation in this stage. In this study, we used the rodent malaria parasite Plasmodium berghei and showed that an AP2-family transcription factor, designated AP2-L, plays a critical role in the liver-stage development of the parasite. AP2-L-depleted parasites proliferated normally in blood and in mosquitoes. However, the ability of these parasites to infect the liver was approximately 10,000 times lower than that of wild-type parasites. In vitro assays showed that the sporozoites of these parasites invaded hepatocytes normally but that their development stopped in the middle of the liver schizont stage. Expression profiling using transgenic P. berghei showed that fluorescent protein-tagged AP2-L increased rapidly during the liver schizont stage but suddenly disappeared with the formation of the mature liver schizont. DNA microarray analysis showed that the expression of several genes, including those of parasitophorous vacuole membrane proteins, was significantly decreased in the early liver stage of AP2-L-depleted parasites. Investigation of the targets of this transcription factor should greatly promote the exploration of liver-stage antigens and the elucidation of the mechanisms of hepatocyte infection by malaria parasites.
url http://europepmc.org/articles/PMC3492389?pdf=render
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AT tomomikato identificationofanap2familyproteinthatiscriticalformalarialiverstagedevelopment
AT masaoyuda identificationofanap2familyproteinthatiscriticalformalarialiverstagedevelopment
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