PMID- 30581113
OWN - NLM
STAT- MEDLINE
DCOM- 20190314
LR  - 20200930
IS  - 1934-6069 (Electronic)
IS  - 1931-3128 (Linking)
VI  - 25
IP  - 1
DP  - 2019 Jan 9
TI  - PfVPS45 Is Required for Host Cell Cytosol Uptake by Malaria Blood Stage 
      Parasites.
PG  - 166-173.e5
LID - S1931-3128(18)30592-4 [pii]
LID - 10.1016/j.chom.2018.11.010 [doi]
AB  - During development in human erythrocytes, the malaria parasite Plasmodium 
      falciparum internalizes a large part of the cellular content of the host cell. 
      The internalized cytosol, consisting largely of hemoglobin, is transported to the 
      parasite's food vacuole where it is degraded, providing nutrients and space for 
      growth. This host cell cytosol uptake (HCCU) is crucial for parasite survival but 
      the parasite proteins mediating this process remain obscure. Here, we identify 
      P. falciparum VPS45 as an essential factor in HCCU. Conditional inactivation of 
      PfVPS45 led to an accumulation of host cell cytosol-filled vesicles within the 
      parasite and inhibited the delivery of hemoglobin to the parasite's digestive 
      vacuole, resulting in arrested parasite growth. A proportion of these HCCU 
      vesicle intermediates was positive for phosphatidylinositol 3-phosphate, 
      suggesting endosomal characteristics. Thus PfVPS45 provides insight into the 
      elusive machinery of the ingestion pathway in a parasite that contains an 
      endolysosomal system heavily repurposed for protein secretion.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Jonscher, Ernst
AU  - Jonscher E
AD  - Molecular Biology and Immunology Section, Bernhard Nocht Institute for Tropical 
      Medicine, Bernhard Nocht Strasse 74, Hamburg 20359, Germany.
FAU - Flemming, Sven
AU  - Flemming S
AD  - Molecular Biology and Immunology Section, Bernhard Nocht Institute for Tropical 
      Medicine, Bernhard Nocht Strasse 74, Hamburg 20359, Germany.
FAU - Schmitt, Marius
AU  - Schmitt M
AD  - Molecular Biology and Immunology Section, Bernhard Nocht Institute for Tropical 
      Medicine, Bernhard Nocht Strasse 74, Hamburg 20359, Germany.
FAU - Sabitzki, Ricarda
AU  - Sabitzki R
AD  - Molecular Biology and Immunology Section, Bernhard Nocht Institute for Tropical 
      Medicine, Bernhard Nocht Strasse 74, Hamburg 20359, Germany.
FAU - Reichard, Nick
AU  - Reichard N
AD  - Molecular Biology and Immunology Section, Bernhard Nocht Institute for Tropical 
      Medicine, Bernhard Nocht Strasse 74, Hamburg 20359, Germany.
FAU - Birnbaum, Jakob
AU  - Birnbaum J
AD  - Molecular Biology and Immunology Section, Bernhard Nocht Institute for Tropical 
      Medicine, Bernhard Nocht Strasse 74, Hamburg 20359, Germany.
FAU - Bergmann, Barbel
AU  - Bergmann B
AD  - Molecular Biology and Immunology Section, Bernhard Nocht Institute for Tropical 
      Medicine, Bernhard Nocht Strasse 74, Hamburg 20359, Germany.
FAU - Hohn, Katharina
AU  - Hohn K
AD  - Electron Microscopy Unit, Bernhard Nocht Institute for Tropical Medicine, 
      Bernhard Nocht Strasse 74, Hamburg 20359, Germany.
FAU - Spielmann, Tobias
AU  - Spielmann T
AD  - Molecular Biology and Immunology Section, Bernhard Nocht Institute for Tropical 
      Medicine, Bernhard Nocht Strasse 74, Hamburg 20359, Germany. Electronic address: 
      spielmann@bni-hamburg.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181220
PL  - United States
TA  - Cell Host Microbe
JT  - Cell host & microbe
JID - 101302316
RN  - 0 (Hemoglobins)
RN  - 0 (Protozoan Proteins)
SB  - IM
CIN - Trends Parasitol. 2019 May;35(5):333-335. PMID: 31003757
MH  - Animals
MH  - Biological Transport
MH  - Cytosol/metabolism/*parasitology
MH  - Erythrocytes/*parasitology
MH  - Golgi Apparatus/metabolism
MH  - Hemoglobins/*metabolism
MH  - Host-Parasite Interactions
MH  - Humans
MH  - Malaria, Falciparum/*blood/*parasitology
MH  - Parasites/growth & development
MH  - Plasmodium falciparum/growth & development/pathogenicity/*physiology
MH  - Protein Transport
MH  - Protozoan Proteins/genetics/*metabolism
MH  - Vacuoles/metabolism/parasitology/ultrastructure
OTO - NOTNLM
OT  - Plasmodium falciparum
OT  - VPS45
OT  - endocytosis
OT  - hemoglobin
OT  - host cell cytosol uptake
OT  - malaria
OT  - molecular parasitology
EDAT- 2018/12/26 06:00
MHDA- 2019/03/15 06:00
CRDT- 2018/12/25 06:00
PHST- 2018/06/26 00:00 [received]
PHST- 2018/10/01 00:00 [revised]
PHST- 2018/11/19 00:00 [accepted]
PHST- 2018/12/26 06:00 [pubmed]
PHST- 2019/03/15 06:00 [medline]
PHST- 2018/12/25 06:00 [entrez]
AID - S1931-3128(18)30592-4 [pii]
AID - 10.1016/j.chom.2018.11.010 [doi]
PST - ppublish
SO  - Cell Host Microbe. 2019 Jan 9;25(1):166-173.e5. doi: 10.1016/j.chom.2018.11.010. 
      Epub 2018 Dec 20.