NUP221

NUP221 (PF3D7_0905100) is a nucleoporin component of the nuclear pore complex (NPC) in Plasmodium parasites, identified as part of the NPC macromolecular assembly through bioinformatic and genetic characterization, with the P. falciparum protein recognized from its P. berghei ortholog (PMID:30050042). In P. berghei, NUP221 localizes around the nucleus and is arranged in a rosette structure around the centriolar plaque during blood-stage asexual replication, and it undergoes turnover/exchange within intact NPCs during this replication, indicating that NPC formation and homeostasis proceed without nuclear envelope breakdown (PMID:39526784). Beyond its membership in the NPC and this replication-associated turnover behavior, no NUP221-specific molecular function, binding partners, or structural detail have been characterized in the available corpus.

1. 2018 Medium

   Establishing which parasite proteins build the NPC was the first step; identifying NUP221 as a nucleoporin placed it within the NPC macromolecular assembly.

   Evidence Bioinformatic identification with genetic tagging and localization, plus cryo electron tomography of Plasmodium NPCs, with the P. falciparum ortholog inferred from P. berghei

   PMID:30050042

   Open questions at the time

   • No NUP221-specific molecular activity or binding partners defined
   • Functional role of NUP221 within the NPC not tested
   • Assignment of the P. falciparum gene rests on orthology to P. berghei
2. 2024 High

   Whether NPCs are static or remodeled during closed mitosis was unresolved; showing NUP221 turnover within intact pores established that NPC homeostasis occurs without nuclear envelope breakdown during asexual replication.

   Evidence U-ExM localization plus a RITE (recombination-induced tag exchange) turnover assay adapted to P. berghei via a single-plasmid Cre-recombinase tagging system

   PMID:39526784

   Open questions at the time

   • Not demonstrated in P. falciparum
   • Molecular mechanism and machinery driving NUP221 exchange unknown
   • Functional consequence of blocking NUP221 turnover not tested

• The molecular function of NUP221 beyond NPC membership and its turnover behavior remains undefined, including its interaction partners, structural placement within the pore, and any phenotype upon loss of function.
• No direct binding partners or subcomplex assignment for NUP221
• No loss-of-function or essentiality data
• No P. falciparum-specific functional characterization