Fig. 5.

Critical Rab and SNARE proteins participate in degradative and secretory autophagy. In degradative autophagy, Rab8b and STX17 are essential for autophagosomes to attract lysosomes for fusion and form autolysosomes for cargo degradation. On the other hand, three modes of secretory autophagy are proposed to mediate cargo release. First, MVB fuses with autophagosomes to form amphisomes mediated by Rab11 and then transport to PM via Rab8a- and Rab27a-mediated route. Most cargoes such as Wnt5A, MMP2, IL-6, IL-8, annexin A2, galectin-1, HMGB1, type I collagen and fibronectin, are believed to be secreted via MVB-dependent secretory autophagy. Second, IL-1β-carrying autophagosomes can be directly transported to PM with the help of SNAP23/29 and STX3/4. Of note, Sec22B is involved in both the secretory autophagy pathways. The last one is mediated via secretory lysosomes. Autophagosomes fusing with lysosomes are able to facilitate the secretion of histamine, β-hexosaminidase and cathepsin K