USO1p115

USO1p115, also known as p115, is a 115-kilodalton cytosolic tethering factor involved in the early secretory pathway. It is encoded by the USO1 gene in humans and functions as a Rab1 GTPase effector that coordinates ER-to-Golgi transport by tethering transport vesicles to the cis-Golgi network, thereby facilitating the docking and subsequent SNARE-mediated fusion of vesicles.

Mechanism and interactions: p115 binds Rab1-GTP on ER-derived vesicles and interacts with Golgi matrix proteins such as GM130 and giantin. These interactions help capture vesicles at the cis-Golgi and promote the assembly of SNARE complexes necessary for membrane fusion. p115 is thought to function as a dimer through its coiled-coil region, contributing to its elongated, tethering architecture.

Structure and localization: The protein is a predominantly cytosolic, elongated coiled-coil molecule of approximately 115 kDa. It is recruited to ER-Golgi intermediate compartments and the cis-Golgi by Rab1 and partner tethering factors, with localization that is dynamic in accordance with trafficking activity.

Evolution and orthology: USO1/p115 is conserved across eukaryotes, with yeast Uso1p serving as its functional ortholog. Despite species differences, the core role in ER-to-Golgi tethering is preserved, and domain organization supports its tethering function.

Clinical significance: Proper p115 function is essential for efficient secretory trafficking. Disruption of p115-mediated tethering can impair vesicle docking and cargo transport, potentially affecting Golgi structure and overall cellular secretion.

In summary, USO1p115 is a central Rab1-dependent tethering factor that facilitates ER-to-Golgi transport and maintains efficient secretory pathway function.