The Plasmodium falciparum Artemisinin Susceptibility-Associated AP-2 Adaptin mu Subunit is Clathrin Independent and Essential for Schizont Maturation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F20%3A00537501" target="_blank" >RIV/60077344:_____/20:00537501 - isvavai.cz</a>

Výsledek na webu

<a href="https://mbio.asm.org/content/11/1/e02918-19" target="_blank" >https://mbio.asm.org/content/11/1/e02918-19</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1128/mBio.02918-19" target="_blank" >10.1128/mBio.02918-19</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Plasmodium falciparum Artemisinin Susceptibility-Associated AP-2 Adaptin mu Subunit is Clathrin Independent and Essential for Schizont Maturation

Popis výsledku v původním jazyce

The efficacy of current antimalarial drugs is threatened by reduced susceptibility of Plasmodium falciparum to artemisinin, associated with mutations in pfkelch13. Another gene with variants known to modulate the response to artemisinin encodes the mu subunit of the AP-2 adaptin trafficking complex. To elucidate the cellular role of AP-2 mu in P. falciparum, we performed a conditional gene knockout, which severely disrupted schizont organization and maturation, leading to mislocalization of key merozoite proteins. AP-2 mu is thus essential for blood-stage replication. We generated transgenic P. falciparum parasites expressing hemagglutinin-tagged AP-2 mu and examined cellular localization by fluorescence and electron microscopy. Together with mass spectrometry analysis of coimmunoprecipitating proteins, these studies identified AP-2 mu-interacting partners, including other AP-2 subunits, the K10 kelch-domain protein, and PfEHD, an effector of endocytosis and lipid mobilization, but no evidence was found of interaction with clathrin, the expected coat protein for AP-2 vesicles. In reverse immunoprecipitation experiments with a clathrin nanobody, other heterotetrameric AP-complexes were shown to interact with clathrin, but AP-2 complex subunits were absent.

Název v anglickém jazyce

The Plasmodium falciparum Artemisinin Susceptibility-Associated AP-2 Adaptin mu Subunit is Clathrin Independent and Essential for Schizont Maturation

Popis výsledku anglicky

The efficacy of current antimalarial drugs is threatened by reduced susceptibility of Plasmodium falciparum to artemisinin, associated with mutations in pfkelch13. Another gene with variants known to modulate the response to artemisinin encodes the mu subunit of the AP-2 adaptin trafficking complex. To elucidate the cellular role of AP-2 mu in P. falciparum, we performed a conditional gene knockout, which severely disrupted schizont organization and maturation, leading to mislocalization of key merozoite proteins. AP-2 mu is thus essential for blood-stage replication. We generated transgenic P. falciparum parasites expressing hemagglutinin-tagged AP-2 mu and examined cellular localization by fluorescence and electron microscopy. Together with mass spectrometry analysis of coimmunoprecipitating proteins, these studies identified AP-2 mu-interacting partners, including other AP-2 subunits, the K10 kelch-domain protein, and PfEHD, an effector of endocytosis and lipid mobilization, but no evidence was found of interaction with clathrin, the expected coat protein for AP-2 vesicles. In reverse immunoprecipitation experiments with a clathrin nanobody, other heterotetrameric AP-complexes were shown to interact with clathrin, but AP-2 complex subunits were absent.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

mBio

ISSN

2150-7511

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

e02918-19

Kód UT WoS článku

000518763400047

EID výsledku v databázi Scopus

2-s2.0-85079850964