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. 2015 Oct 12;211(1):123–144. doi: 10.1083/jcb.201311117

Figure 1.

Figure 1.

Models of cargo trafficking through APPL and EEA1 compartments. (A) In model 1, the APPL compartment serves as an intermediate en route to EEA1-positive endosomes. Cargo first binds to receptors on the PM and is internalized via CDE or CIE. The CDE includes formation of CCPs and internalization CCVs. Some CCVs acquire APPL1 or fuse with APPL1 membranes. Other CCVs and CIV directly fuse with EEA1 endosomes. APPL1 vesicles directly (10% through an APPL1+EEA1 double-positive endocytic intermediate [A & E]) or indirectly (47%+43%) convert into EEA1 endosomes. Cargo can be recycled to the surface via recycling endosomes (RE) or transported to late endosomes (LE) and lysosomes for degradation. Blue and red arrows demark transport of Tf and EGF, respectively. Black arrows, steps that must be common for both cargos. (B) In model 2, APPL1 endosomes that were not accounted in the literature (43%) constitute a stable endocytic compartment. These endosomes sort cargo for recycling and bi-directionally exchange of cargo with EEA1 endosomes through APPL1+EEA1 double-positive endosomes. Transition to late endocytic compartment occurs through EEA1 by conversion mechanism.