A role for a PDZ protein in the early secretory pathway for the targeting of proTGF-α to the cell surface

In general, plasma membrane integral proteins, such as the membrane-anchored growth factor proTGF-alpha, are assumed to be transported to the cell surface via a nonregulated, constitutive pathway. proTGF-alpha C-terminal mutants are retained in an early secretory compartment. Here, using a two-hybrid screen, we identify two TACIPs (pro (T) under bar GF-(a) under bar lpha (c) under bar ytoplasmic domain-(i) under bar nteracting (p) under bar roteins) that contain PDZ domains and do not interact with proTGF-alpha. C-terminal mutants. The binding specificity of one of them, TACIP18 (previously identified and named Syntenin or mda-g), coincides with that of the component that possibly mediates the normal trafficking of proTGF-alpha. TACIP18 colocalizes and interacts specifically with immature, intracellular forms of proTGF-alpha. Therefore, it appears that the interaction of TACIP18 with proTGF-alpha in the early secretory pathway is necessary for the targeting of the latter to the cell surface.