FIGURE 7:

Model of SHRC interaction with retromer on membranes. (A) We propose that the CSC of the retromer is recruited to the endosomal membrane through mechanisms involving GTP-bound Rab 7 and cargo proteins that are destined to enter the retromer-mediated sorting pathway. When retromer accumulates to high density on the endomembrane, the SHRC is then recruited through cumulative binding of higher-affinity (*) and lower-affinity FAM21 repeats with VPS35 proteins, thus facilitating the cargo enrichment process and promoting subsequent F-actin–mediated maturation of the retromer subdomain, vesicle scission, and trafficking. (B) Bird's-eye view of the process discussed in A after initial recruitment of the SHRC via FAM21-mediated interactions with VPS35.