scholarly journals Babesia divergens Apical Membrane Antigen 1 and Its Interaction with the Human Red Blood Cell

2009 ◽  
Vol 77 (11) ◽  
pp. 4783-4793 ◽  
Author(s):  
Estrella Montero ◽  
Marilis Rodriguez ◽  
Yelena Oksov ◽  
Cheryl A. Lobo
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Apical Membrane ◽  
Vital Role ◽  
Red Cell ◽  
Electron Microscopic ◽  
Red Cell Membrane ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Babesia Divergens

ABSTRACT Multiple parasite ligand-erythrocyte receptor interactions must occur for successful Babesia and Plasmodium invasion of the human red cell. One such parasite ligand is the apical membrane antigen 1 (AMA1) which is a conserved apicomplexan protein present in the micronemes and then secreted onto the surface of the merozoite. Much evidence exists for a vital role for AMA1 in host cell invasion; however, its interaction with the host erythrocyte has remained controversial. In this paper, we present a detailed characterization of a Babesia divergens homolog of AMA1 (BdAMA1), and taking advantage of the relatively high amounts of native BdAMA1 available from the parasite culture system, show that proteolytic products of native BdAMA1 bind to a trypsin- and chymotrypsin-sensitive receptor on the red blood cell. Moreover, immuno-electron microscopic images of the B. divergens merozoite captured during invasion offer additional evidence of the presence of BdAMA1 on the red cell membrane. Given the importance of AMA1 in invasion and the central role invasion plays in pathogenesis, these studies have implications both for novel drug design and for the development of new vaccine approaches aimed at interfering with AMA1 function.

scholarly journals Apical Membrane Antigen 1, a Major Malaria Vaccine Candidate, Mediates the Close Attachment of Invasive Merozoites to Host Red Blood Cells

2004 ◽  
Vol 72 (1) ◽  
pp. 154-158 ◽  
Author(s):  
G. H. Mitchell ◽  
A. W. Thomas ◽  
G. Margos ◽  
A. R. Dluzewski ◽  
L. H. Bannister
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Candidate ◽  
Apical Membrane ◽  
Plasmodium Knowlesi ◽  
Red Cells ◽  
Red Cell ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Malaria Vaccine Candidate ◽  
Candidate Molecule

ABSTRACT Apical membrane antigen 1 (AMA-1) of Plasmodium merozoites is established as a candidate molecule for inclusion in a human malaria vaccine and is strongly conserved in the genus. We have investigated its function in merozoite invasion by incubating Plasmodium knowlesi merozoites with red cells in the presence of a previously described rat monoclonal antibody (MAb R31C2) raised against an invasion-inhibitory epitope of P. knowlesi AMA-1 and then fixing the material for ultrastructural analysis. We have found that the random, initial, long-range (12 nm) contact between merozoites and red cells occurs normally in the presence of the antibody, showing that AMA-1 plays no part in this stage of attachment. Instead, inhibited merozoites fail to reorientate, so they do not bring their apices to bear on the red cell surface and do not make close junctional apical contact. We conclude that AMA-1 may be directly responsible for reorientation or that the molecule may initiate the junctional contact, which is then presumably dependent on Duffy binding proteins for its completion.

scholarly journals Phosphorylation of the red blood cell membrane during the active transport of C++.

1976 ◽  
Vol 67 (2) ◽  
pp. 251-261 ◽  
Author(s):  
Y N Cha ◽  
K S Lee
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Transport Mechanism ◽  
Initial Reaction ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Red Blood Cell Membrane ◽  
Ca Transport ◽  
Phosphorylation Reaction

The phosphorylation of red blood cell membrane fragments (RBCMF) during Ca++ transport was investigated. When red cell membrane fragments are incubated with [gamma-32P]ATP under the experimental condition which minimizes the phosphorylation of Na+-K+-ATPase, RBCMF are labeled in the presence of Mg++ without Ca++. When Ca++ is added, the labeling decreases due to dephosphorylation of RBCMF. The initial reaction of phosphorylation is reversed in the presence of excess ADP. The treatment of RBCMF with n-ethylmaleimide (NEM) does not interfere with the initial phosphorylation reaction, but blocks the dephosphorylation in the presence of Ca++. These data suggest that the enzymatic sequence of the Ca++ transport mechanism may be very similar to that of the Na+ transport mechanism.

Red blood cell as glucose carrier: significance for placental and cerebral glucose transfer

1984 ◽  
Vol 246 (3) ◽  
pp. R289-R298 ◽  
Author(s):  
J. A. Jacquez
Keyword(s):  
Blood Cell ◽  
Glucose Transport ◽  
Blood Brain Barrier ◽  
Red Blood Cell ◽  
High Capacity ◽  
Brain Barrier ◽  
Fetal Life ◽  
Red Cell Membrane ◽  
Glucose Transfer ◽  
Blood Brain

At plasma glucose values of 5 mM (90 mg/100 ml) the maximum glucose transport capacity of the human red cell membrane is 12,000 times the rate of glucose utilization by the red blood cell. Mammals, other than primates, that have been tested have a comparable high-capacity system during fetal life, which is lost soon after birth. It has been suggested that the availability of the water space of the red blood cell for distribution of glucose facilitates transfer across the placenta during fetal life in all mammals and across the blood-brain barrier in adult primates. Though plausible, more comparative studies of glucose transport in red blood cells of other species and direct experimental evaluations of the contribution of the red blood cell to glucose transfer across the placenta and the blood-brain barrier are needed.

scholarly journals Expression, Purification, and Biological Characterization of Babesia microti Apical Membrane Antigen 1

2015 ◽  
Vol 83 (10) ◽  
pp. 3890-3901 ◽  
Author(s):  
Prasun Moitra ◽  
Hong Zheng ◽  
Vivek Anantharaman ◽  
Rajdeep Banerjee ◽  
Kazuyo Takeda ◽  
...  
Keyword(s):  
Apical Membrane ◽  
The United States ◽  
Host Cells ◽  
Health Concern ◽  
Babesia Microti ◽  
Type I ◽  
Content Type ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Extracellular Region

The intraerythrocytic apicomplexanBabesia microti, the primary causative agent of human babesiosis, is a major public health concern in the United States and elsewhere. Apicomplexans utilize a multiprotein complex that includes a type I membrane protein called apical membrane antigen 1 (AMA1) to invade host cells. We have isolated the full-lengthB. microtiAMA1 (BmAMA1) gene and determined its nucleotide sequence, as well as the amino acid sequence of the AMA1 protein. This protein contains an N-terminal signal sequence, an extracellular region, a transmembrane region, and a short conserved cytoplasmic tail. It shows the same domain organization as the AMA1 orthologs from piroplasm, coccidian, and haemosporidian apicomplexans but differs from all other currently known piroplasmida, including otherBabesiaandTheileriaspecies, in lacking two conserved cysteines in highly variable domain III of the extracellular region. Minimal polymorphism was detected in BmAMA1 gene sequences of parasite isolates from six babesiosis patients from Nantucket. Immunofluorescence microscopy studies showed that BmAMA1 is localized on the cell surface and cytoplasm near the apical end of the parasite. Native BmAMA1 from parasite lysate and refolded recombinant BmAMA1 (rBmAMA1) expressed inEscherichia colireacted with a mouse anti-BmAMA1 antibody using Western blotting.In vitrobinding studies showed that both native BmAMA1 and rBmAMA1 bind to human red blood cells (RBCs). This binding is trypsin and chymotrypsin treatment sensitive but neuraminidase independent. Incubation ofB. microtiparasites in human RBCs with a mouse anti-BmAMA1 antibody inhibited parasite growth by 80% in a 24-h assay. Based on its antigenically conserved nature and potential role in RBC invasion, BmAMA1 should be evaluated as a vaccine candidate.

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