MYR4

MYR4 is a Toxoplasma gondii parasitophorous vacuole (PV) protein that functions as a component of the machinery translocating dense granule effectors across the PV membrane into the host cell (PMID:32075880). It was identified as a MYR1-interacting partner by reciprocal co-immunoprecipitation and mass spectrometry, physically linking it to the known MYR translocation apparatus at the PV (PMID:32075880). Genetic loss of MYR4 abolishes translocation of the effector GRA16 into the host cell and prevents the downstream host response of c-Myc and cyclin E1 upregulation, establishing MYR4 as required for effector export and effector-driven host remodeling (PMID:32075880). Beyond its PV localization, its interaction with MYR1, and its requirement for GRA16 export, no further mechanistic detail — including its precise biochemical role in the translocation process — has been characterized in the available corpus.

1. 2020 Medium

   Whether additional proteins besides MYR1 form the effector translocation apparatus was unresolved; identifying MYR4 as a MYR1-interacting PV protein defined a new component of this machinery.

   Evidence Affinity purification / reciprocal co-immunoprecipitation of MYR1 followed by mass spectrometry, in T. gondii GT1

   PMID:32075880

   Open questions at the time

   • Stoichiometry and architecture of the MYR1-MYR4 complex not defined
   • Whether the interaction is direct or bridged by other proteins not established
2. 2020 Medium

   Whether MYR4 is functionally required for effector export was unknown; loss-of-function showed it is essential for GRA16 translocation and the resulting host c-Myc/cyclin E1 upregulation, establishing its role in effector-driven host remodeling.

   Evidence Genetic knockout with GRA16 translocation assay and host c-Myc/cyclin E1 readout, in T. gondii GT1

   PMID:32075880

   Open questions at the time

   • Whether MYR4 is required for translocation of effectors other than GRA16 not tested
   • Biochemical step in translocation controlled by MYR4 unknown
3. 2020 Low

   Localizing MYR4 to the PV placed it physically at the site where effectors cross the PV membrane, consistent with a direct translocation role.

   Evidence Subcellular localization inferred from affinity purification context, in T. gondii GT1

   PMID:32075880

   Open questions at the time

   • PV localization inferred from affinity purification rather than confirmed by direct high-resolution imaging in this record
   • Whether MYR4 spans or associates with the PV membrane not resolved

• The precise molecular mechanism by which MYR4 promotes effector passage across the PV membrane, and the full set of effectors it exports, remain undefined.
• No structural model of the MYR translocation apparatus
• No biochemical activity assigned to MYR4
• Effector repertoire dependent on MYR4 beyond GRA16 uncharacterized