LAP5

LAP5 (PF3D7_1451600) is a member of the LCCL lectin adhesive-like protein (LAP) complex of Plasmodium that functions in the crystalloid organelle during the mosquito-stage transition of the parasite (PMID:23684590, PMID:19932717). In P. berghei, LAP5 mRNA is transcribed in sexual blood-stage (gametocyte) parasites, but its protein is not detected at that stage, indicating that translational repression delays LAP5 protein accumulation until after gametogenesis (PMID:23684590). Following fertilization, in the ookinete and early oocyst stages, LAP5 is recruited into the LAP complex, joining the pre-formed LAP1/LAP2/LAP3 sub-complex chiefly through the SRCR modules of LAP1, and localizes to the crystalloid organelle (PMID:28414172, PMID:23684590, PMID:19932717). Beyond its membership in this complex and its crystalloid targeting, no LAP5-specific molecular activity or phenotype has been characterized in the available corpus; the wider ~50-protein LAP interactome and the complex's role in crystalloid biogenesis are established at the level of other LAP members rather than through direct functional study of LAP5 itself (PMID:32736136).

1. 2009 Low

   Establishing where LAP5 acts within the parasite was the first requirement for placing it in a cellular process; tagging showed LAP5 is targeted to the crystalloid organelle in ookinetes and early oocysts.

   Evidence Fluorescent protein tagging and live-cell microscopy in transgenic P. berghei

   PMID:19932717

   Open questions at the time

   • LAP5 mentioned as one of two additional family members without individual functional follow-up
   • No functional consequence of crystalloid localization tested for LAP5 specifically
   • Mechanism of crystalloid targeting not defined
2. 2013 Medium

   The disconnect between LAP5 transcript and protein levels answered how its expression is timed: translational repression withholds LAP5 protein in gametocytes and delays accumulation until the crystalloid-forming stages.

   Evidence GFP-tagging of PbLAP5 with fluorescence microscopy plus transcript-versus-protein comparison in transgenic P. berghei

   PMID:23684590

   Open questions at the time

   • The molecular machinery mediating LAP5 translational repression is not identified
   • No demonstration of a LAP5 loss-of-function phenotype
   • Timing of protein onset defined by localization rather than quantitative protein kinetics
3. 2017 Medium

   How LAP5 assembles into the complex was resolved by showing it is recruited post-fertilization into a pre-formed LAP1/LAP2/LAP3 sub-complex, chiefly via LAP1 SRCR modules, ordering the assembly hierarchy.

   Evidence Affinity purification of reporter-tagged LAPs with label-free quantitative mass spectrometry in transgenic P. berghei

   PMID:28414172

   Open questions at the time

   • Direct LAP1-LAP5 binding interface not structurally mapped
   • Whether LAP5 recruitment is required for complex function untested
   • Contribution of LAP5 to complex stability not measured
4. 2020 Low

   Broadening the complex context, LAP5 was placed within an extended ~50-protein interactome including CPW-WPC and pleckstrin homology-like domain proteins, situating the LAP complex in a larger assembly linked to crystalloid targeting and biogenesis.

   Evidence GFP affinity pulldown of LAP3::GFP with high-accuracy mass spectrometry and crystalloid co-localization microscopy in transgenic P. berghei

   PMID:32736136

   Open questions at the time

   • LAP5 identified only as a complex member; no direct functional experiment on LAP5 in this study
   • Interactome derived from LAP3-GFP pulldown, not LAP5 bait
   • Which interactome members contact LAP5 directly is unknown

• It remains unknown what LAP5 contributes to the LAP complex on its own — whether its loss affects crystalloid biogenesis, oocyst division, or sporozoite formation, and what its LCCL-domain-based molecular activity is.
• No LAP5-specific gene disruption or phenotype reported in the corpus
• No biochemical activity assigned to the LAP5 LCCL/lectin-like domains
• All functional inference derives from other LAP members or the complex as a whole