AP1 And Trans-Golgi Network Contribute To The Formation Of Autophagosomes

Despite recent advances in understanding the functions of autophagy in developmental and pathological conditions, the underlying mechanism of where and how autophagosomal structures acquire membrane remains enigmatic. Here, we provide evidence that post-Golgi membrane traffic plays a critical role in autophagosome formation. Increased secretory of constitutive cargoes from the trans-Golgi network (TGN)-to-plasma membrane induced the formation of microtubμle-associated protein light chain 3 (LC3)-positive structures. At the early phase of autophagy, LC3 associated with and then budded off from a distinct TGN domain without constitutive TGN-to-plasma cargoes and TGN-to-endosome proteins. Activator protein 1 (AP1), a clathrin adaptor, localized to starvation- and rapamycin-induced autophagosomes. Dysfunction of AP1-dependent clathrin coating at the TGN but not the plasma membrane prevented autophagy. Our results thus suggest an essential role of the TGN in autophagy, providing LC3-bound membrane to autophagosomes through an AP1-dependent pathway.