TRIM50 Interacts with Microtubules to Facilitate Vesicle Trafficking in Gastric Parietal Cells

The tripartite motif (TRIM) family of proteins consist of over 75 different genes and serve as regulators of many critical aspects of health and disease including, wound healing, secretion, and apoptosis. Our lab showed previously that MG53, a member of the TRIM-family proteins, played an essential role in repair cell membrane injury. TRIM50 is the closest homologue to MG53 and has dissimilar cellular function. The molecular mechanisms that underlie the different functions for MG53 and TRIM50 are unknown. We know that TRIM50 is predominantly expressed in the stomach, and participates in vesicle trafficking during acid secretion in gastric parietal cells. Recently, our lab has shown MG53 vesicle trafficking is driven by the molecular motor non-muscle myosin II-A. In this study, we used intracellular vesicle tracking to identify how TRIM50 associated vesicles move within the cell, distinguishing between diffusive and directional ballistic motion. We demonstrated that vesicles associated with TRIM50 do not exhibit diffusive motion; rather, they exhibit directed motion, which requires microtubules. Additionally, we showed that TMK-1 cells expressing TRIM50 treated with microtubule inhibitors nocodazole or colchicine abolished the directed motion of the TRIM50-associated vesicles. We also performed a pull-down assay to identify the molecular motor that drives TRIM50 trafficking. Overall, our data suggest TRIM50-associated vesicles are associated with dynein, a microtubule-associated molecular motor, to power vesicle trafficking related to acid secretion in gastric parietal cells. This study provides a clue in how TRIM50 is involved in vesicle trafficking and how the deletion of TRIM50 involved in the gastrointestinal issues observed in patients with Williams Syndrome.