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

In general, plasma membrane integral proteins, such as the membrane-anchore d growth factor proTGF-alpha, are assumed to be transported to the cell sur face via a nonregulated, constitutive pathway. proTGF-alpha C-terminal muta nts are retained in an early secretory compartment. Here, using a two-hybri d 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 rotei ns) that contain PDZ domains and do not interact with proTGF-alpha. C-termi nal mutants. The binding specificity of one of them, TACIP18 (previously id entified and named Syntenin or mda-g), coincides with that of the component that possibly mediates the normal trafficking of proTGF-alpha. TACIP18 col ocalizes and interacts specifically with immature, intracellular forms of p roTGF-alpha. Therefore, it appears that the interaction of TACIP18 with pro TGF-alpha in the early secretory pathway is necessary for the targeting of the latter to the cell surface.