Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle.

Kinesins are microtubule (MT)-based motors important in cell division, motility, polarity, and intracellular transport in many eukaryotes. However, they are poorly studied in the divergent eukaryotic pathogens Plasmodium spp., the causative agents of malaria, which manifest atypical aspects of cell...

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Main Authors: Mohammad Zeeshan, Ravish Rashpa, David J P Ferguson, Steven Abel, Zeinab Chahine, Declan Brady, Sue Vaughan, Carolyn A Moores, Karine G Le Roch, Mathieu Brochet, Anthony A Holder, Rita Tewari
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-07-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001704&type=printable
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author Mohammad Zeeshan
Ravish Rashpa
David J P Ferguson
Steven Abel
Zeinab Chahine
Declan Brady
Sue Vaughan
Carolyn A Moores
Karine G Le Roch
Mathieu Brochet
Anthony A Holder
Rita Tewari
author_facet Mohammad Zeeshan
Ravish Rashpa
David J P Ferguson
Steven Abel
Zeinab Chahine
Declan Brady
Sue Vaughan
Carolyn A Moores
Karine G Le Roch
Mathieu Brochet
Anthony A Holder
Rita Tewari
author_sort Mohammad Zeeshan
collection DOAJ
description Kinesins are microtubule (MT)-based motors important in cell division, motility, polarity, and intracellular transport in many eukaryotes. However, they are poorly studied in the divergent eukaryotic pathogens Plasmodium spp., the causative agents of malaria, which manifest atypical aspects of cell division and plasticity of morphology throughout the life cycle in both mammalian and mosquito hosts. Here, we describe a genome-wide screen of Plasmodium kinesins, revealing diverse subcellular locations and functions in spindle assembly, axoneme formation, and cell morphology. Surprisingly, only kinesin-13 is essential for growth in the mammalian host while the other 8 kinesins are required during the proliferative and invasive stages of parasite transmission through the mosquito vector. In-depth analyses of kinesin-13 and kinesin-20 revealed functions in MT dynamics during apical cell polarity formation, spindle assembly, and axoneme biogenesis. These findings help us to understand the importance of MT motors and may be exploited to discover new therapeutic interventions against malaria.
format Article
id doaj-art-c59ab74510044eb5b8416d04d84d4899
institution Kabale University
issn 1544-9173
1545-7885
language English
publishDate 2022-07-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Biology
spelling doaj-art-c59ab74510044eb5b8416d04d84d48992025-08-20T03:56:00ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-07-01207e300170410.1371/journal.pbio.3001704Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle.Mohammad ZeeshanRavish RashpaDavid J P FergusonSteven AbelZeinab ChahineDeclan BradySue VaughanCarolyn A MooresKarine G Le RochMathieu BrochetAnthony A HolderRita TewariKinesins are microtubule (MT)-based motors important in cell division, motility, polarity, and intracellular transport in many eukaryotes. However, they are poorly studied in the divergent eukaryotic pathogens Plasmodium spp., the causative agents of malaria, which manifest atypical aspects of cell division and plasticity of morphology throughout the life cycle in both mammalian and mosquito hosts. Here, we describe a genome-wide screen of Plasmodium kinesins, revealing diverse subcellular locations and functions in spindle assembly, axoneme formation, and cell morphology. Surprisingly, only kinesin-13 is essential for growth in the mammalian host while the other 8 kinesins are required during the proliferative and invasive stages of parasite transmission through the mosquito vector. In-depth analyses of kinesin-13 and kinesin-20 revealed functions in MT dynamics during apical cell polarity formation, spindle assembly, and axoneme biogenesis. These findings help us to understand the importance of MT motors and may be exploited to discover new therapeutic interventions against malaria.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001704&type=printable
spellingShingle Mohammad Zeeshan
Ravish Rashpa
David J P Ferguson
Steven Abel
Zeinab Chahine
Declan Brady
Sue Vaughan
Carolyn A Moores
Karine G Le Roch
Mathieu Brochet
Anthony A Holder
Rita Tewari
Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle.
PLoS Biology
title Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle.
title_full Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle.
title_fullStr Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle.
title_full_unstemmed Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle.
title_short Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle.
title_sort genome wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle
url https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001704&type=printable
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