Yeast Atg40 has a domain structure similar to mammalian FAM134B, yet it
localizes to the tubular ER, like RTN3L. In yeast, the sheets and tubules in the
cytoplasm, and at the cell cortex, are referred to as the cortical ER. Atg40 is
largely present on the cortical ER, while Atg39 is principally localized in the
nuclear envelope. Atg40, which contains a reticulon-like domain, recruits Atg8
via a LIR motif to initiate cortical macro-ER-phagy. Autophagosome-driven
fragmentation of the cortical ER occurs at ER-phagy sites (ERPHS) with the aid
of the Lst1-Sec23 complex. In contrast, transport vesicles bud from the ER at ER
exit sites (ERES), where the COPII coat complex is assembled. Soluble secretory
cargo proteins are loaded into vesicles via a receptor-mediated process, while
transmembrane cargo proteins interact with the COPII coat subunits or specific
adaptors.