Figure 7.

(A) PtdIns(3)P and PtdIns(3,5)P₂ most likely recruit Atg18 to two distinct membrane compartments, where it is required for autophagy (PAS) and regulation of organelle morphology (vacuole), respectively. On the vacuole, we envision Atg18 acting as a “sensor” of PtdIns(3,5)P₂, continually cycling between the cytosol (Atg18^CYTO) and the limiting membrane (Atg18^VAC) in response to changes in phosphoinositide levels. One function of Atg18 on the membrane is to inhibit the Fab1 kinase, thus establishing a negative feedback loop. This circuit forms the integral part of an elegant system that allows dynamic control of vacuole morphology. (B) Model for Atg18 function as it cycles on and off the vacuole membrane. During and after recruitment by the phospholipid PtdIns(3,5)P₂, Atg18 also associates with Vac7 and Vac17. Atg18 may indirectly regulate activity of the Fab1 kinase by sequestering Vac7. Vac17 most likely functions as a myosin-specific adapter for Atg18, thus enabling retrograde membrane transport from the vacuole along actin tracks. Membrane deformation could be directly or indirectly mediated by Atg18, e.g., via recruitment of an as-of-yet unidentified fission factor.