Fig. 4. Models of BLOC-1–AP-3 sorting functions. (A,B) Two different vesicles, A and B, fuse with a target organelle (right). VAMP7-TI is present in vesicle A (blue cylinder). Its cognate Q-(t)-SNAREs (syntaxin 7, 8 and Vti1b; orange cylinders) are present in the target organelle. Model A depicts AP-3 and BLOC-1 complexes co-residing in vesicle A (Salazar et al., 2006). In this vesicle, BLOC-1 may regulate the recognition of specific cargoes, like the SNARE VAMP7-TI, either by bridging AP-3 and a selected membrane protein (interactions 2 and 3) or by stabilizing specific AP-3–cargo interactions (interactions 1 and 2). Interactions 1 (Martinez-Arca et al., 2003) and 2 have been documented (Di Pietro et al., 2006) and (G. Salazar and V.F., unpublished results). Interaction 3 is speculative. On the target membrane a tripartite Q-(t)-SNARE complex of syntaxin 7, syntaxin 8, and Vti1b is maintained by BLOC-1, independently of AP-3. Model B depicts the selective sorting of SNAREs or tissue-specific cargo into vesicle B by the BLOC-1 complex. Vesicle B represents a vesicle population distinct from vesicle A. Sorting into and/or biogenesis of vesicle B requires BLOC-1 but not AP-3 function. Model A and model B are non-exclusive. Either Model A alone or a combination of models A and B explain both the convergent sorting phenotypes of BLOC-1 and AP-3 deficiencies as well as the altered colocalization between syntaxins 7 and 8, which is unique to BLOC-1–mutant cells (Salazar et al., 2006).