Fig 6. Model for FRAT and TMEM98 interaction.

Schematic representation of possible TMEM98 topologies and trafficking activities based on in silico prediction algorithms and our experimental data. Given that most algorithms predict TMEM98 to be a single-pass transmembrane protein and our data confirm that the C-terminus of the protein is located on the extracellular surface, model A (left) is the most likely scenario. However, it would require TMEM98 and FRAT to interact in the endosomal compartment, for which no evidence is available to date. The alternative model B (right) assumes the presence of a second transmembrane domain, to allow exposure of a cytosolic FRAT-binding domain. Depiction of the endosomal trafficking and sorting compartments is based on the previously reported association of different Rab proteins with specific endosomal domains [40,52–55].