NUP138

PF3D7_0903500 (NUP138) is an FG-repeat-containing nucleoporin of the Plasmodium nuclear pore complex (NPC) that localizes to the nuclear periphery throughout the parasite life cycle (PMID:30050042). It was identified as an NPC component by bioinformatic prediction combined with endogenous genetic tagging in P. berghei, where it is described as the smallest known FG-repeat nucleoporin (PMID:30050042, PMID:36040030), and its NPC membership has been corroborated by TurboID proximity labeling and mass spectrometry of the NPC proximity proteome (PMID:36040030). High-resolution ultrastructure expansion microscopy shows NUP138 distributed around the nucleus across the 24-hour blood-stage replication cycle and organized into a rosette around the centriolar plaque during mitosis (PMID:39526784, PMID:38405843). In P. falciparum, NUP138 co-purifies with the cryptochrome-like protein PfDPL alongside other nucleoporins (NUP313, NUP637, NUP176) and chromatin-remodelling and cytoskeletal proteins (PMID:41986327). Beyond this structural membership in the NPC, no enzymatic activity, structural model, or dedicated functional role has been characterized for NUP138 in the available corpus.

1. 2018 Medium

   Establishing whether Plasmodium encodes recognizable nucleoporins was the first step in defining the parasite NPC; identifying NUP138 as an FG-repeat nucleoporin placed it structurally within the pore.

   Evidence Bioinformatic prediction plus endogenous genetic tagging and immunofluorescence localization in P. berghei, with cryo-electron tomography of Plasmodium NPCs

   PMID:30050042

   Open questions at the time

   • No functional mutagenesis or knockout to test whether NUP138 is required for NPC assembly or nucleocytoplasmic transport
   • No in vitro reconstitution or structural placement of NUP138 within the pore scaffold
   • FG-repeat function (barrier/transport role) not directly demonstrated for NUP138
2. 2022 Medium

   Confirming NUP138 as a bona fide pore component and a reliable spatial reference required an in vivo functional read-out; TurboID fused at the endogenous locus validated its nuclear-periphery position and its utility as an NPC bait.

   Evidence Endogenous C-terminal TurboID fusion with streptavidin-based proximity labeling and mass spectrometry of the NPC proximity proteome in P. berghei

   PMID:36040030

   Open questions at the time

   • Proximity labeling reports neighborhood, not direct binary interactions or stoichiometry within the NPC
   • Single-lab data
   • Does not resolve which NPC subcomplex NUP138 belongs to
3. 2024 Medium

   Whether NUP138 distribution changes with the cell cycle was unknown; high-resolution imaging showed it persists at the nuclear envelope throughout blood-stage replication and forms a rosette around the centriolar plaque during mitosis, linking NUP138 to the mitotic spindle-pole region.

   Evidence Endogenous smHA-3xHA tagging and ultrastructure expansion microscopy (U-ExM) with NHS ester staining in P. berghei

   PMID:38405843 PMID:39526784

   Open questions at the time

   • Functional significance of the centriolar-plaque rosette not tested
   • No mechanism linking NUP138 to spindle-pole or mitotic function
   • Single-lab observation
4. 2026 Low

   Whether NUP138 associates with factors beyond the core pore was tested by co-purification, placing it in a P. falciparum complex containing PfDPL, other nucleoporins, and chromatin/cytoskeletal proteins.

   Evidence Affinity purification coupled to mass spectrometry using PfDPL as bait in P. falciparum

   PMID:41986327

   Open questions at the time

   • Single co-purification with NUP138 as one of many co-purified proteins; no reciprocal or direct interaction validation for NUP138
   • No functional follow-up on NUP138 within this complex
   • Physiological relevance of the PfDPL association to NUP138 undefined

• The functional role of NUP138 beyond structural NPC membership remains undefined: no loss-of-function phenotype, transport role, or mechanistic contribution to the mitotic rosette has been established.
• No knockout, knockdown, or conditional-depletion phenotype for NUP138
• No demonstrated role in nucleocytoplasmic transport or NPC assembly
• No structural model or defined subcomplex assignment