Oligomerization supports transport of a mutant secretory protein out of the endoplasmic reticulum.

To examine the transport of the single subunits of the glycoprotein complex gp80 (clusterin, apolipoprotein J), a marker protein for apical exocytosis and main secretory product of Madin-Darby canine kidney (MDCK) cells, several mutant cDNAs were constructed and expressed in the fibroblastic baby hamster kidney (BHK-21) cell line. In the absence of the second subunit the mutant proteins formed disulfide-linked homodimeric complexes. In the homodimeric form lys-gp45, a lysozyme-tagged mutant representing the C-terminal subunit, acquired competence for transport to the cell surface. Biogenesis and transport of this hybrid protein were also examined in stably transfected MDCK cells. In these cells which express both the endogenous gene and the mutant cDNA lys-gp45 was linked via disulfide bonds to the gp80 complex. These heterooligomeric complexes were secreted predominantly at the apical cell surface. Thus, oligomerization regardless of whether it resulted in homodimeric or heterooligomeric complexes conveyed transport competence to the mutant protein.