TI - ULK/Atg1 and focal adhesion components . AB - We have demonstrated that FIP200 localizes to the autophagic isolation membrane and is essential for autophagy . We do not think that FIP200 is an autophagy-specific protein . The most striking evidence for this is that FIP200-/- mice die between E13.5 and 16.5 with defective heart and liver development , whereas autophagy-deficient Atg5-/- and Atg7-/- mice survive embryogenesis ( although they die within one day of birth ) . Indeed , FIP200 involvement has been suggested in various cellular processes , such as inhibition of Pyk2 -induced signaling , inhibition of cell migration through FAK inhibition , tumor suppression , induction of RB expression , cell size regulation through inhibition of the TSC complex , inhibition of p53-mediated G1-S progression and inhibition of TNF -induced apoptosis , probably through inhibition with ASK1 and TRAF2 . These data suggest that FIP200 is a multifunctional protein . An important question is whether FIP200 alone or FIP200 and its interacting proteins are involved in autophagy . While we were preparing this manuscript , a D.melanogaster genetic analysis revealed a genetic interaction between Atg1 and paxillin , a cytoskeletal scaffolding protein . The study further demonstrates that paxillin and vinculin redistribute from focal adhesions to intracellular structures under starvation conditions and that paxillin-deficient MEFs are defective in autophagy . In contrast , our analysis showed that FAK is not required for autophagy , suggesting that the focal adhesion complex per se is not involved in autophagy . FAK-independent communication between FIP200 and paxillin will be the subject of future studies in both autophagy and focal adhesion . Given that atleast three of the focal adhesion components function in autophagy , it is possible that ULKs also plays a role in cell adhesion that is independent of its function in autophagy . Indeed , GFP-ULK1 and -ULK2 were occasionally detected at the cell periphery ( Fig S2 ) , and overexpression of wild-type ULKs caused abnormal cell morphology such as cell rounding and protrusion ( Fig S3 ) . So far , several studies have suggested autophagy -independent roles of Atg1/ULK in various species , such as axonal elongation and branching in C.elegans and mammals . These functions may be related to the role of Atg1 in focal adhesion . In conclusion , we have identified a novel ULK -interacting protein , FIP200 , which is functionally similar to yeast Atg17 . The ULK-FIP200 complex is essential for autophagy , but the precise role of this complex is unknown . Identification of physiologically relevant SUBstrates of Atg1-ULK is one of the most straightforward approaches , although it has not been successful thus far in any species studied ( Deminoff and Herman , 2007 ) . Searching for additional interacting proteins will also facilitate understanding of the role of Atg1-ULK complex and the regulation of autophagy induction and autophagosome formation .