FIGURE 3 Secretory autophagy: an unconventional secretory pathway. In contrast to conventional secretion where proteins are traf fi cked through the ER-Golgi, proteins can also enter the autophagosome through the ER or directly from the ERGIC together with the membrane that forms the autophagosome. TMED10 together with the chaperones HSP90A and HSP90B1 have been shown to allow protein cargo to enter the ERGIC post- translationally.TRIM16recruitsIL1BdirectlytotheLC3labelledmembranesforsecretion.Autophagosomecargocaneitherbedirectlyreleased by fusion with the plasma membrane (A) or be released following lysosomal fusion where R-SNARE Sec22 on the autophagosome/autolysosome membrane delivers the vesicle speci fi cally to the plasma membrane where it interacts with syntaxins (STX) 3 or 4 together with the SNAPs 23 and 29 (B) .Alternativelyfusion oftheautophagosome with multivesicular bodies (MVB) (C) releasescargo within extracellularvesiclesbybindingto STX1 or 2 also with SNAPs 23/29. This is in contrast to secretory lysosomes which release the digestive enzymes of lysosomes using STX3 and SNAP 23. The mechanism of release determines whether the cargo is released intact (A) , digested (B) or within a protective vesicle (C) . See text for more details. Figure was createdbymodifying illustrations fromservier medical art licenced under aCreative Commons Attribution 3.0 Unported License: (http://