Vps26p, a component of retromer, directs the interactions of Vps35p in endosome-to-Golgi retrieval

Endosome-to-Golgi retrieval of the carboxypeptidase Y receptor Vps10p is mediated by a recently discovered membrane coat complex termed retromer. Retromer comprises five conserved proteins: Vps35p, Vps29p, Vps5p, Vps17p, and Vps26p. Vps35p recognizes cargo molecules such as Vps10p and interacts strongly with Vps29p. Vps5p forms a subcomplex with Vps17p and has been proposed to play a structural role by self-assembling into large multimeric structures. The function of Vps26p is currently unknown. We have investigated the role that Vps26p plays in retromer-mediated endosome-to-Golgi transport by analyzing dominant negative alleles of Vps26p. These mutants have identified a crucial region of Vps26p that plays an important role in its function. Functional domains of Vps26p have been investigated by the creation of yeast-mouse hybrid molecules in which domains of Vps26p have been replaced by the similar domain in the protein encoded by the mouse VPS26 gene, H beta 58. These domain swap experiments have shown that Vps26p promotes the interactions between the cargo-selective component Vps35p and the structural components Vps5p/Vps17p.