SRP68

SRP68 (PF3D7_0621900) is one of six polypeptide subunits that, together with a 303 nt SRP RNA, constitute the P. falciparum signal recognition particle ribonucleoprotein complex implicated in protein targeting (PMID:24434517). In asexual blood-stage parasites, GFP-chimera imaging shows SRP68 undergoes nucleo-cytoplasmic shuttling (PMID:24434517), and this trafficking depends on importin α/β-mediated nuclear import: submicromolar ivermectin blocks nuclear import of SRP polypeptides including SRP68 and kills parasites (PMID:24434517). Beyond its membership in the SRP complex and this shuttling behavior, the specific mechanistic role of SRP68 has not been characterized in the available corpus; a single co-IP/MS study also detected it in the cytosolic interactome of PfPRMT5 without functional resolution (PMID:37349497).

1. 2014 Medium

   Establishing whether P. falciparum encodes a canonical SRP machinery answered whether SRP68 exists as a defined complex subunit rather than an isolated protein.

   Evidence GFP-chimera expression and co-localization of six SRP subunits with a 303 nt SRP RNA in transgenic parasites

   PMID:24434517

   Open questions at the time

   • Complex membership inferred from co-localization, not biochemical co-IP or reconstitution
   • Direct role of SRP68 within the complex (e.g. RNA or subunit binding) not resolved
   • No substrate or targeting activity demonstrated for SRP68 itself
2. 2014 Medium

   Determining SRP68's subcellular distribution addressed whether the protein is confined to the cytosol or traffics to the nucleus, an unusual property for an SRP subunit.

   Evidence Live-cell fluorescence microscopy of SRP68-GFP chimera in asexual blood-stage parasites

   PMID:24434517

   Open questions at the time

   • Functional consequence of nuclear shuttling for SRP68 not established
   • Whether shuttling reflects SRP assembly or an independent role is unknown
3. 2014 Medium

   Testing ivermectin sensitivity addressed the mechanism of SRP68 nuclear entry and its druggability, linking shuttling to the importin pathway.

   Evidence Ivermectin treatment of SRP-GFP transgenic lines with imaging of nuclear import and parasite viability assay

   PMID:24434517

   Open questions at the time

   • Direct binding of SRP68 to importin α/β not demonstrated
   • Whether killing is caused specifically by loss of SRP68 nuclear import versus broader effects is unresolved
4. 2023 Low

   Interactome profiling of PfPRMT5 asked whether SRP68 associates with the arginine methyltransferase machinery, hinting at a possible regulatory link.

   Evidence Co-immunoprecipitation/mass spectrometry of the PfPRMT5 cytosolic interactome

   PMID:37349497

   Open questions at the time

   • Single co-IP/MS detection with no reciprocal validation
   • Biological significance of the association not experimentally resolved
   • No evidence SRP68 is a methylation substrate

• The direct molecular function of SRP68 within the SRP complex and the purpose of its nuclear shuttling remain undefined.
• No biochemical reconstitution of SRP68 within the complex
• No identified binding partners within the complex confirmed by direct interaction
• Functional role of nucleo-cytoplasmic shuttling uncharacterized