Figure 4. Model of Atg11 roles in selective autophagy.

A. SAR activation by kinases during selective autophagy - In selective autophagy conditions, SARs bound to cargos are activated by phosphorylation by a kinase, such as Hrr25 or CK2, in their Atg11-binding regions (A11BRs) (phosphorylation is indicated by a red circle labelled P). Prior to SAR activation, Atg11 is mostly monomeric and cytosolic. Note that under nutrient-rich conditions (vegetative growth), Atg13 hyper-phosphorylated by the mTOR kinase, has only a weak affinity for Atg1, which corelates with low activity of Atg1 kinase. B. Atg11 recruitment to the activated SAR and cargo recruitment to the PAS - A phospho-activated SAR binds Atg11 to initiate the selective PAS formation. Binding SARs to the C-terminal CC4 of Atg11 promotes its dimerization, allowing recruitment of the cargo to the PAS, which is located adjacent to the vacuole. Independently, Atg1 is recruited to the vacuole by Atg13. Simultaneously, via the interaction between Trs85 and Atg9, the Trs85-containing TRAPPIII complex resides on Atg9-vesicles and facilitates the association of Ypt1 (GTP-bound and active) on Atg9-vesicles. C. Atg11-mediated scaffolding events at the PAS - Atg11 activated by the SAR also recruits to the PAS the following: 1) Atg9-vesicles with active Ypt1 via its interactions with Atg9, Ypt1 and possibly Trs85. 2) The Atg17 scaffold complex, composed of Atg17, Atg31 and Atg29, via its interaction with phosphorylated Atg29. 3) At the vacuole, due to Atg1-Atg11 association, Atg1 can bind to and cluster on the cargo to become active. These events allow the spatial and temporal activation of selective autophagy. D. Both Atg11 and the Atg17 complexes scaffold the core autophagy machinery - It remains unclear whether Atg11 and Atg17 form mutually-exclusive complexes with Atg1. E. Steps orchestrated at the PAS by active Atg1 kinase, including initiation of phagophore membrane formation - Active Atg1 kinase recruits other core autophagy proteins, including Atg8 conjugated to phosphatidylethanolamine (PE) on the phagophore membrane. By using pre-existing scaffolding of Atg11 and Atg17, Atg1 contributes to tight vesicle tethering, initiating phagophore formation. F. COPII vesicle recruitment to the PAS for phagophore expansion - In starvation-induced autophagy, efficient phagophore expansion requires recruitment to the PAS of not only Atg9-vesicles, but also COPII vesicles. Hrr25 can also be recruited to the PAS in an Atg9-independent manner on COPII vesicles. It is unknown if Atg11 recruits Hrr25 also on COPII vesicles, as Atg17 does. The precise role of Hrr25 at the PAS is enigmatic. G. Initiation of membrane curvature and expansion of the phagophore membrane – The interaction of Atg11 with the Atg20-Snx4 complex recruits the PtdIns3P-enriched membranes and stabilizes phagophore curvature. The Atg17 complex and Atg11-Atg20-Snx4 at the PAS contribute to the phagophore expansion. H. Phagophore membrane engulfment of cargo - Phagophore expansion continues around the cargo via engaging other activated SARs, which can bind Atg8-PE (the phosphorylation within the AIM is indicated by a pink circle labeled P). At the same time, Atg11 coordinates with the Atg17-Atg31-Atg29 complex (not shown for simplicity) to recruit the Vam7 SNARE and prevent premature membrane fusion. I. Autophagosome completion, dissociation of protein components and autophagosome-vacuole fusion - In the final step, detachment of Atg11 and other autophagy machinery components initiates autophagosome-vacuole fusion using autophagosomal and vacuolar SNARE proteins described in the main text.