TRXL2

TrxL2 is a microtubule inner protein (MIP) that lines the luminal surface of the cortical microtubules of Toxoplasma gondii, where it stabilizes the tubulin lattice (PMID:34031406). It was first identified as a novel member of a multi-protein complex coating the cortical microtubules, recovered through coimmunoprecipitation of TrxL1-associated proteins, to which it is a close homolog (PMID:23873863). Cryo-EM of ex vivo cortical microtubules established TrxL2, together with TrxL1 and SPM1, as bona fide MIPs that form a mesh on the luminal microtubule surface and simultaneously reinforce the lattice in both longitudinal and lateral directions (PMID:34031406). Genetic deletion of these MIPs, including TrxL2, compromises microtubule stability and integrity under detergent and cold challenge, defining its role in cortical microtubule robustness (PMID:34031406). Beyond its structural role as a lattice-stabilizing MIP, no additional biochemical activity of TrxL2 has been characterized in the available corpus.

1. 2013 Medium

   Establishing whether TrxL2 associates with the cortical cytoskeleton, its identification as a member of the TrxL1-associated cortical microtubule complex placed it physically within a microtubule-coating assembly.

   Evidence Coimmunoprecipitation of TrxL1-associated proteins followed by mass spectrometry in Toxoplasma gondii

   PMID:23873863

   Open questions at the time

   • Single Co-IP/MS identification without reciprocal validation or direct functional characterization of TrxL2
   • Does not resolve whether TrxL2 binds microtubules directly or indirectly via the complex
   • No localization defined at the luminal versus outer microtubule surface
2. 2021 High

   To determine where TrxL2 sits on the microtubule and what it contributes structurally, cryo-EM resolved it as a luminal microtubule inner protein and deletion assays showed it is required for lattice stability.

   Evidence Single-particle cryo-EM of ex vivo cortical microtubules plus genetic MIP deletion with detergent/cold stability assays in Toxoplasma gondii

   PMID:34031406

   Open questions at the time

   • Individual contribution of TrxL2 versus TrxL1 and SPM1 to the stabilizing mesh is not separated
   • Mechanism of TrxL2 recruitment into the microtubule lumen is unknown
   • Whether TrxL2 retains any thioredoxin-like enzymatic activity is not addressed

• How TrxL2 is targeted into the microtubule lumen and whether it has any biochemical activity beyond its structural MIP role remain open.
• No recruitment or assembly mechanism defined
• No enzymatic or redox activity tested
• Contribution to parasite morphology or motility not established in the corpus