MSP10

MSP10 (PF3D7_0620400) is a GPI-anchored merozoite surface protein of Plasmodium falciparum that participates in erythrocyte invasion during the blood stage (PMID:12615336, PMID:15820753). It carries a signal peptide and a C-terminal GPI-attachment site, partitions into the detergent phase upon Triton X-114 fractionation, and is displayed in an apical distribution on the surface of trophozoites, schizonts, and free merozoites (PMID:12615336); GPI modification was independently confirmed by glucosamine metabolic labeling, placing MSP10 among the GPI-anchored schizont/merozoite proteome (PMID:16603573). The protein undergoes limited proteolytic processing, detected as ~80 kDa and ~36 kDa species (PMID:12615336). Functionally, MSP10 engages the erythrocyte surface: synthetic peptides spanning the sequence bind human erythrocytes in a saturable, enzyme-sensitive manner, recognize a 50 kDa erythrocyte membrane protein, and inhibit merozoite invasion (PMID:15820753). Its two C-terminal EGF-like domains are surface-accessible targets whose antibodies inhibit parasite growth in vitro (PMID:26174014), and MSP10 directly binds the invasion ligand PfGAMA through its N-terminal R1 region, with anti-R1 antibodies inhibiting growth (PMID:31824483). In the ortholog P. vivax, the C-terminal EGF-containing region binds reticulocytes but not normocytes, a binding blocked by EGF-domain-derived peptides (PMID:33562650).

1. 2003 Medium

   Establishing MSP10 as a bona fide surface protein was the first step, defining where and when it acts during the blood stage and whether it is membrane-attached.

   Evidence RT-PCR, stage-specific immunoblot, Triton X-114 phase fractionation, and immunofluorescence in P. falciparum

   PMID:12615336

   Open questions at the time

   • Functional consequence of the 80 kDa to 36 kDa processing not defined
   • Protease responsible for cleavage not identified
2. 2005 Medium

   To ask whether MSP10 contributes to invasion mechanistically, peptides were tested for erythrocyte binding, showing the protein engages a specific host receptor and that this engagement is functionally required.

   Evidence Synthetic peptide-erythrocyte binding assays with neuraminidase/trypsin/chymotrypsin sensitivity and in vitro invasion inhibition in P. falciparum

   PMID:15820753

   Open questions at the time

   • The 50 kDa erythrocyte receptor was not molecularly identified
   • Peptide binding may not reflect binding by the full-length folded protein
3. 2006 High

   Whether the earlier Triton X-114 result truly reflected GPI anchoring was resolved by direct biochemical labeling, confirming MSP10 as a GPI-anchored member of the merozoite surface proteome.

   Evidence Radioactive glucosamine labeling and proteomics in P. falciparum schizonts/merozoites

   PMID:16603573

   Open questions at the time

   • Does not address MSP10's functional role or partners
4. 2015 Medium

   To test whether MSP10's structural domains are exposed and vaccine-relevant, monoclonal antibodies against each EGF-like domain were tested, showing the folds are accessible on the parasite surface and functionally targetable.

   Evidence Growth inhibition assays with recombinant human monoclonal antibodies against EGF domains 1 and 2 in P. falciparum 3D7A, with SPR/ELISA affinity measurement

   PMID:26174014

   Open questions at the time

   • EC50 values in the mg/ml range indicate weak inhibitory potency
   • Mechanism by which anti-EGF antibodies block invasion not defined
5. 2019 High

   Placing MSP10 in a molecular invasion complex, this work identified a direct binding partner and the region mediating the interaction, linking MSP10 to the PfGAMA invasion ligand.

   Evidence Co-immunoprecipitation, surface plasmon resonance, and growth inhibition assays in P. falciparum

   PMID:31824483

   Open questions at the time

   • Functional role of the MSP10-PfGAMA complex during invasion not defined
   • Whether the R1-PfGAMA interaction is required for erythrocyte receptor engagement unknown
6. 2021 Medium

   Extending the host-binding role to a second species, the P. vivax ortholog's C-terminal EGF region was shown to selectively bind reticulocytes, indicating a conserved receptor-engagement function localized to the EGF domains.

   Evidence Protein-cell binding assays, peptide competition, and rosette formation assays with enriched reticulocytes for P. vivax MSP10

   PMID:33562650

   Open questions at the time

   • The reticulocyte receptor for PvMSP10 not identified
   • Species-divergent cell tropism (reticulocyte-selective in P. vivax) not directly compared to the P. falciparum protein

• The identity of the erythrocyte receptor(s) bound by MSP10 and the functional requirement of MSP10 (and its PfGAMA complex) for invasion in vivo remain open.
• The 50 kDa P. falciparum erythrocyte receptor and the P. vivax reticulocyte receptor are unidentified
• No genetic knockout/knockdown phenotype for MSP10 in the corpus
• How MSP10, PfGAMA, and erythrocyte receptor binding are coordinated during invasion is unresolved