Abstract:
:Malaria parasites export 'a secretome' of hundreds of proteins, including major virulence determinants, from their endoplasmic reticulum (ER), past the parasite plasma and vacuolar membranes to the host erythrocyte. The export mechanism is high affinity (nanomolar) binding of a host (cell) targeting (HT) motif RxLxE/D/Q to the lipid phosphatidylinositol 3-phosphate (PI(3)P) in the ER. Cleavage of the HT motif releases the secretory protein from the ER membrane. The HT motif is thought to be the only export signal resident in an N-terminal vacuolar translocation sequence (VTS) that quantitatively targets green fluorescent protein to the erythrocyte. We have previously shown that the R to A mutation in the HT motif, abrogates VTS binding to PI(3)P (K(d)>5 μM). We now show that remarkably, the R to A mutant is exported to the host erythrocyte, for both membrane and soluble reporters, although the efficiency of export is reduced to ~30% of that seen with a complete VTS. Mass spectrometry indicates that the R to A mutant is cleaved at sites upstream of the HT motif. Antibodies to upstream sequences confirm that aberrantly cleaved R to A protein mutant is exported to the erythrocyte. These data suggest that export mechanisms, independent of PI(3)P as well as those dependent on PI(3)P, function together in a VTS to target parasite proteins to the host erythrocyte.
journal_name
Mol Biochem Parasitoljournal_title
Molecular and biochemical parasitologyauthors
Bhattacharjee S,Speicher KD,Stahelin RV,Speicher DW,Haldar Kdoi
10.1016/j.molbiopara.2012.07.004subject
Has Abstractpub_date
2012-10-01 00:00:00pages
106-13issue
2eissn
0166-6851issn
1872-9428pii
S0166-6851(12)00205-8journal_volume
185pub_type
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