RT Journal Article
SR Electronic
T1 LC3B phosphorylation regulates FYCO1 binding and directional transport of autophagosomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.15.081638
DO 10.1101/2020.05.15.081638
A1 Jose L. Nieto-Torres
A1 Sean-Luc Shanahan
A1 Romain Chassefeyre
A1 Sara Landeras-Bueno
A1 Sandra E. Encalada
A1 Malene Hansen
YR 2020
UL http://biorxiv.org/content/early/2020/05/16/2020.05.15.081638.abstract
AB Macroautophagy (hereafter referred to as autophagy) is a conserved process that promotes cellular homeostasis through the degradation of cytosolic components, also known as cargo. During autophagy, cargo is sequestered into double-membrane vesicles called autophagosomes, which are predominantly transported in the retrograde direction to the perinuclear region to fuse with lysosomes, thus ensuring cargo degradation [1]. The mechanisms regulating directional autophagosomal transport remain unclear. The ATG8 family of proteins associate with autophagosome membranes [2] and play key roles in autophagy, such as the movement of autophagosomes. This is achieved via the interaction of ATG8 with adaptor proteins, including FYCO1, a protein involved in the anterograde transport of autophagosomes toward the cell periphery [1,3–5]. We previously reported that phosphorylation of LC3B/ATG8 on threonine 50 (LC3B-T50) by the Hippo kinase STK4 is required for autophagy through unknown mechanisms [6]. Here, we show that LC3B-T50 phosphorylation decreases the interaction between LC3B and FYCO1, which in turn regulates the starvation-induced perinuclear positioning of autophagosomes. Moreover, non-phosphorylatable LC3B-T50A aberrantly switches the predominant retrograde movement of autophagosomes to anterograde movement towards the cell periphery in multiple cell types, including in mouse primary hippocampal neurons. Our data support a role of a nutrient-sensitive STK4–LC3B–FYCO1 axis in the regulation of the directional transport of autophagosomes via the post-translational regulation of LC3B. Given that autophagy is impaired in many human conditions, including neurodegenerative diseases, our findings may highlight new principles of vesicle transport regulation critical for disease etiology.Competing Interest StatementThe authors have declared no competing interest.