Updated Insight into the Physiological and Pathological Roles of the Retromer Complex

Abstract

Retromer complexes mediate protein trafficking from the endosomes to the trans-Golgi network (TGN) or through direct recycling to the plasma membrane. In yeast, they consist of a conserved trimer of the cargo selective complex (CSC), Vps26-Vps35-Vps29 and a dimer of sorting nexins (SNXs), Vps5-Vps17. In mammals, the CSC interacts with different kinds of SNX proteins in addition to the mammalian homologues of Vps5 and Vps17, which further diversifies retromer functions. The retromer complex plays important roles in many cellular processes including restriction of invading pathogens. In this review, we summarize some recent developments in our understanding of the physiological and pathological functions of the retromer complex.

Keywords: disease; endosome; receptors; retromer; vacuolar protein sorting.

Figure 1

Schematic representation of retromer-mediated Vps10 sorting at the vacuole. Missorted Vps10 cargoes at the endosomes reach the vacuole and are rescued from degradation via retromer-mediated sorting at the vacuolar membrane and delivered to the early endosome for further sorting to the Golgi.

Figure 2

Recruitment of retromer to the endosome and the fission of the vesicle after its exit from the endosome. Activated Rab5 and Rab7 (Rab5-GTP and Rab7-GTP, respectively) recruit the SNX and CSC subcomplexes, respectively, to the endosomal membrane. The retromer subcomplexes assemble into a complete retromer complex and concentrate cargoes following membrane tubulation by the SNX proteins, and subsequent vesicle scission. Further fission of the vesicle occurs downstream of its endosome exit for cargoes taking different itineraries.