P125 is a novel mammalian Sec23p-interacting protein with structural similarity to phospholipid-modifying proteins

COPII-coated vesicles are involved in protein transport from the endoplasmi c reticulum to the Gels apparatus. COPII consists of three parts: Sar1p and the two protein complexes, Sec23p-Sec24p and Sec13p-Sec31p. Using a glutat hione S-transferase fusion protein with mouse Sec23p, we identified a novel mammalian Sec23p-interacting protein, p125, which is clearly distinct from Sec24p. The N-terminal region of p125 is rich in proline residues, and the central and C-terminal regions exhibit significant homology to phospholipi d-modifying proteins, especially phosphatidic acid preferring-phospholipase A(1). We transiently expressed p125 and mouse Sec23p in mammalian cells an d examined their interaction. The results showed that the N-terminal region of p125 is important for the interaction with Sec23p, We confirmed the int eraction between the two proteins by a yeast two-hybrid assay. Overexpressi on of p125, like that of mammalian Sec23p, caused disorganization of the en doplasmic reticulum-Golgi intermediate compartment and Gels apparatus, sugg esting its role in the early secretory pathway.