PMID- 31491036
OWN - NLM
STAT- MEDLINE
DCOM- 20200207
LR  - 20210110
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 15
IP  - 9
DP  - 2019 Sep
TI  - The Plasmodium falciparum rhoptry bulb protein RAMA plays an essential role in 
      rhoptry neck morphogenesis and host red blood cell invasion.
PG  - e1008049
LID - 10.1371/journal.ppat.1008049 [doi]
LID - e1008049
AB  - The malaria parasite Plasmodium falciparum invades, replicates within and 
      destroys red blood cells in an asexual blood stage life cycle that is responsible 
      for clinical disease and crucial for parasite propagation. Invasive malaria 
      merozoites possess a characteristic apical complex of secretory organelles that 
      are discharged in a tightly controlled and highly regulated order during 
      merozoite egress and host cell invasion. The most prominent of these organelles, 
      the rhoptries, are twinned, club-shaped structures with a body or bulb region 
      that tapers to a narrow neck as it meets the apical prominence of the merozoite. 
      Different protein populations localise to the rhoptry bulb and neck, but the 
      function of many of these proteins and how they are spatially segregated within 
      the rhoptries is unknown. Using conditional disruption of the gene encoding the 
      only known glycolipid-anchored malarial rhoptry bulb protein, rhoptry-associated 
      membrane antigen (RAMA), we demonstrate that RAMA is indispensable for blood 
      stage parasite survival. Contrary to previous suggestions, RAMA is not required 
      for trafficking of all rhoptry bulb proteins. Instead, RAMA-null parasites 
      display selective mislocalisation of a subset of rhoptry bulb and neck proteins 
      (RONs) and produce dysmorphic rhoptries that lack a distinct neck region. The 
      mutant parasites undergo normal intracellular development and egress but display 
      a fatal defect in invasion and do not induce echinocytosis in target red blood 
      cells. Our results indicate that distinct pathways regulate biogenesis of the two 
      main rhoptry sub-compartments in the malaria parasite.
FAU - Sherling, Emma S
AU  - Sherling ES
AUID- ORCID: 0000-0002-8339-7060
AD  - Malaria Biochemistry Laboratory, The Francis Crick Institute, London, United 
      Kingdom.
FAU - Perrin, Abigail J
AU  - Perrin AJ
AUID- ORCID: 0000-0001-6682-4297
AD  - Malaria Biochemistry Laboratory, The Francis Crick Institute, London, United 
      Kingdom.
FAU - Knuepfer, Ellen
AU  - Knuepfer E
AD  - Malaria Parasitology Laboratory, The Francis Crick Institute, London, United 
      Kingdom.
FAU - Russell, Matthew R G
AU  - Russell MRG
AUID- ORCID: 0000-0003-4608-7669
AD  - Electron Microscopy Science Technology Platform, The Francis Crick Institute, 
      London, United Kingdom.
FAU - Collinson, Lucy M
AU  - Collinson LM
AD  - Electron Microscopy Science Technology Platform, The Francis Crick Institute, 
      London, United Kingdom.
FAU - Miller, Louis H
AU  - Miller LH
AD  - Laboratory of Malaria and Vector Research, National Institute of Allergy and 
      Infectious Diseases, National Institutes of Health, Rockville, Maryland, United 
      States of America.
FAU - Blackman, Michael J
AU  - Blackman MJ
AUID- ORCID: 0000-0002-7442-3810
AD  - Malaria Biochemistry Laboratory, The Francis Crick Institute, London, United 
      Kingdom.
AD  - Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical 
      Medicine, London, United Kingdom.
LA  - eng
GR  - 106239/Z/14/A/WT_/Wellcome Trust/United Kingdom
GR  - FC001043/WT_/Wellcome Trust/United Kingdom
GR  - FC001043/CRUK_/Cancer Research UK/United Kingdom
GR  - FC001043/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 103459/Z/14/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190906
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Membrane Proteins)
RN  - 0 (Protozoan Proteins)
RN  - 0 (rhoptry associated protein, Plasmodium)
SB  - IM
MH  - Antigens, Protozoan/immunology
MH  - Erythrocytes/*parasitology
MH  - Host-Parasite Interactions/*physiology
MH  - Humans
MH  - Malaria/metabolism
MH  - Malaria, Falciparum/metabolism
MH  - Membrane Proteins/metabolism
MH  - Merozoites/metabolism
MH  - Organelles/metabolism
MH  - Plasmodium falciparum/metabolism
MH  - Protein Transport/physiology
MH  - Protozoan Proteins/*metabolism
PMC - PMC6750612
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/09/07 06:00
MHDA- 2020/02/08 06:00
PMCR- 2019/09/06
CRDT- 2019/09/07 06:00
PHST- 2019/05/27 00:00 [received]
PHST- 2019/08/27 00:00 [accepted]
PHST- 2019/09/18 00:00 [revised]
PHST- 2019/09/07 06:00 [pubmed]
PHST- 2020/02/08 06:00 [medline]
PHST- 2019/09/07 06:00 [entrez]
PHST- 2019/09/06 00:00 [pmc-release]
AID - PPATHOGENS-D-19-00959 [pii]
AID - 10.1371/journal.ppat.1008049 [doi]
PST - epublish
SO  - PLoS Pathog. 2019 Sep 6;15(9):e1008049. doi: 10.1371/journal.ppat.1008049. 
      eCollection 2019 Sep.