Abstract
Although numerous linear motifs that direct protein trafficking within cells have been identified, there are few examples of linear sorting signals mediating directed export of membrane proteins from the Golgi complex to the plasma membrane. The reovirus fusion-associated small transmembrane proteins are simple, single-pass transmembrane proteins that traffic through the endoplasmic reticulum-Golgi pathway to the plasma membrane, where they induce cell-cell membrane fusion. Here we show that a membrane-proximal, polybasic motif (PBM) in the cytosolic tail of p14 is essential for efficient export of p14 from the Golgi complex to the plasma membrane. Extensive mutagenic analysis reveals that the number, but not the identity or position, of basic residues present in the PBM dictates p14 export from the Golgi complex, with a minimum of three basic residues required for efficient Golgi export. Results further indicate that the tribasic motif does not affect plasma membrane retention of p14. Furthermore, introduction of the tribasic motif into a Golgi-localized, chimeric ERGIC-53 protein directs export from the Golgi complex to the plasma membrane. The p14 PBM is the first example of an autonomous, tribasic signal required for Golgi export to the plasma membrane.