A gene-family encoding small exported proteins is conserved across Plasmodium genus

The malaria parasite invades the terminally differentiated erythrocytes, where it grows and multiplies surrounded by a parasitophorous vacuole. Plasmodium blood stages translocate newly synthesized proteins outside the parasitophorous vacuole and direct them to various erythrocyte compartments, including the cytoskeleton and the plasma membrane. Here, we show that the remodeling of the host cell directed by the parasite also includes the recruitment of dematin, an actin-binding protein of the erythrocyte membrane skeleton and its repositioning to the parasite. Internalized dematin was found associated with Plasmodium 14-3-3, which belongs to a family of conserved multitask molecules. We also show that, in vitro, the dematin-14-3-3 interaction is strictly dependent on phosphorylation of dematin at Ser 124 and Ser 333 , belonging to two 14-3-3 putative binding motifs. This study is the first report showing that a component of the erythrocyte spectrin-based membrane skeleton is recruited by the malaria parasite following erythrocyte infection.The Plasmodium parasite, the etiologic agent of malaria, invades the host red blood cell (RBC), 2 where it grows and multiplies within a parasitophorous vacuole (PV). The PV membrane (PVM) represents an interface between the parasite and the host erythrocyte. A subset of parasite proteins is exported beyond the PVM by a recently discovered secretory system directed by a pentameric amino acid sequence motif (PEXE(L/H)T) (1, 2). Additional pathways might flank this unusual export machinery because a number of parasite proteins that do not contain the PEXE(L/H)T motif are also exported to erythrocyte sites (3). The parasite generates novel membrane compartments to sustain protein trafficking. For example, in Plasmodium falciparum-infected RBCs (iRBCs), the so-called Maurer's clefts, organelles anchored to the RBC cytoskeleton, are responsible for the assembly and targeting of parasite adhesive proteins to the erythrocyte surface. Exported proteins are routed to different erythrocyte compartments, including the host membrane skeleton, leading to extensive remodeling of the host cell.The erythrocyte skeleton is anchored to the phospholipid bilayer through two major protein bridges; one connects the integral membrane protein band 3 to spectrin via ankyrin, whereas the other involves the junctional complex, which connects the C-terminal end of spectrin to short actin protofilaments (4, 5). Protein 4.1, dematin, and adducin are components of the junctional complex. Protein 4.1, p55, and the transmembrane glycophorin C form a well characterized ternary complex, which tethers the junctional complex to the plasma membrane (6). The membrane receptors glucose transporter-1 GLUT1 (7) and Band 3 (8) directly bind to dematin and/or adducin, providing alternative links to the erythrocyte plasma membrane.Several P. falciparum exported proteins bring about coordinated remodeling of the spectrin-based erythrocyte membrane skeleton (3, 9). One of the best characterized examples is the knob-associa...

show abstract

“…This was confirmed (Fig. 1C) by double fluorescence, using antibodies against the PVM-resident SEP/ETRAMP family member Pb-SEP1 (20).…”

Section: Expression and Immunolocalization Of P Berghei 14-3-3-supporting

confidence: 60%

Dematin, a Component of the Erythrocyte Membrane Skeleton, Is Internalized by the Malaria Parasite and Associates with Plasmodium 14-3-3

Lalle¹,

Currà²,

Ciccarone³

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite such high biological variation between replicates, the genes encoding the early gametocyte markers Pfg27 (PF13 0011) and Pfs16 (PFD0310w) were readily detected as upregulated, and were present amongst the eight genes. The remaining six coded for two heat shock proteins (PFI0875, PF08 0054), three nonannotated hypothetical proteins (PF10 0164, PF14 0744, PF13 0338), and one member of the PfSep protein family [23] (PF11 0040). The entire data set was also inspected for expression levels of genes encoding known sexual stagespecific proteins which appear at later stages of gametocyte maturation, such as Pfs45/48 and Pfs230, produced since stage II gametocytes [24], Pftubulin-␣II and Pfg377, since stage III [25,26], Pfs230II, specific for stage V male gametocytes [27], and Pfs25, appearing in gametes [28].…”

Section: Pairwise Comparison Of 3d7 and F12 Transcriptomesmentioning

confidence: 99%

“…This group of gene products might suggest a role for signalling and post-translational modifications in the major cytoskeletal rearrangements accompanying transition from stage I to stage II gametocytes. Finally, presence of three of the seven members of the P. falciparum sep gene family, encoding conserved proteins transported to the erythrocyte cytoplasm both in the rodent and the human parasites [23] might suggest involvement of protein trafficking in such rearrangements. Other annotated genes, however, encoded molecules, which do not play obvious roles in sexual differentiation, such as three merozoite surface proteins and one erythrocyte and one retyculocyte binding antigens.…”

Section: Analysis Of the Gene Cluster Upregulated In 3d7 Parasitesmentioning

confidence: 99%

Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum

Silvestrini

Bozdech

Lanfrancotti

et al. 2005

Molecular and Biochemical Parasitology

Self Cite

147

148

View full text Add to dashboard Cite

A genome-wide expression analysis was undertaken to identify novel genes specifically activated from early stages of gametocytogenesis in Plasmodium falciparum. A comparative analysis was conducted on sexually induced cultures of reference parasite clone 3D7 and its gametocyteless derivative clone F12. Competitive hybridisations on long-oligomer microarrays representing 4488 P. falciparum genes identified a remarkably small number of transcripts differentially produced in the two clones. Upregulation of the mRNAs for the early gametocyte markers Pfs16 and Pfg27 was however readily detected in 3D7, and such genes were used as reference transcripts in a comparative time course analysis of 3D7 and F12 parasites between 30 and 40 h post-invasion in cultures induced to enter gametocytogenesis. One hundred and seventeen genes had expression profiles which correlated to those of pfs16 and pfg27, and Northern blot analysis and published proteomic data identified those whose expression was gametocyte-specific. Immunofluorescence analysis with antibodies against two of these gene products identified two novel parasite membrane associated, sexual stage-specific proteins. One was produced from stage I gametocytes and the second showed peak production in stage II gametocytes. The two proteins were named Pfpeg-3 and Pfpeg-4, for P. falciparum proteins of early gametocytes.

show abstract

“…Like Pfmc-2tm and Pfst-2tm, stevor, sep/etramps, and rif genes are located predominantly within subtelomeric regions of chromosomes and encode basic proteins. RIFINs have been detected at the erythrocyte surface (Kyes et al 1999), STEVORs (Kaviratne et al 2002) are Maurer's cleft transmembrane proteins, and SEP/ETRAMPs have been localized to the parasitophorous vacuole membrane (PVM; Spielmann et al 2003) and/or the MCs (Birago et al 2003).…”

Section: A Superfamily Of Two-transmembrane Proteinsmentioning

confidence: 99%

A Plasmodium Gene Family Encoding Maurer's Cleft Membrane Proteins: Structural Properties and Expression Profiling

Sam‐Yellowe

Florens²,

Johnson³

et al. 2004

Genome Res.

141

136

View full text Add to dashboard Cite

Upon invasion of the erythrocyte cell, the malaria parasite remodels its environment; in particular, it establishes a complex membrane network, which connects the parasitophorous vacuole to the host plasma membrane and is involved in protein transport and trafficking. We have identified a novel subtelomeric gene family in Plasmodium falciparum that encodes 11 transmembrane proteins localized to the Maurer's clefts. Using coimmunoprecipitation and shotgun proteomics, we were able to enrich specifically for these proteins and detect distinct peptides, allowing us to conclude that four to 10 products were present at a given time. Nearly all of the Pfmc-2tm genes are transcribed during the trophozoite stage; this narrow time frame of transcription overlaps with the specific stevor and rif genes that are differentially expressed during the erythrocyte cycle. The description of the structural properties of the proteins led us to manually reannotate published sequences, and to detect potentially homologous gene families in both P. falciparum and Plasmodium yoelii yoelii, where no orthologs were predicted uniquely based on sequence similarity. These basic proteins with two transmembrane domains belong to a larger superfamily, which includes STEVORs and RIFINs

show abstract

A gene-family encoding small exported proteins is conserved across Plasmodium genus

Cited by 33 publications

References 27 publications

Dematin, a Component of the Erythrocyte Membrane Skeleton, Is Internalized by the Malaria Parasite and Associates with Plasmodium 14-3-3

Dematin, a Component of the Erythrocyte Membrane Skeleton, Is Internalized by the Malaria Parasite and Associates with Plasmodium 14-3-3

Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum

A Plasmodium Gene Family Encoding Maurer's Cleft Membrane Proteins: Structural Properties and Expression Profiling

Contact Info

Product

Resources

About