RT Journal Article
SR Electronic
T1 ORP1L regulates dynein clustering on endolysosmal membranes in response to cholesterol levels
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.28.273037
DO 10.1101/2020.08.28.273037
A1 Shreyasi Thakur
A1 Peter K. Relich
A1 Elena M. Sorokina
A1 Melike Lakadamyali
YR 2020
UL http://biorxiv.org/content/early/2020/08/29/2020.08.28.273037.abstract
AB The sub-cellular positioning of endolysosomal compartments is crucial for regulating their downstream function. In particular, the positioning of endolysosomes at two sub-cellular locations: the cell periphery versus the cell peri-nuclear region; impacts autophagy, mTOR (mechanistic target of rapamycin) signaling and other cellular processes. Yet, the mechanisms that regulate the trafficking and positioning of endolysosomes at these two sub-cellular locations are poorly understood. Here, using super-resolution microscopy, we show that the retrograde motor dynein forms nano-clusters on endolysosomal membranes. Surprisingly, dynein nano-clusters are larger on peripherally positioned endolysosomes that contain higher cholesterol levels compared to perinuclearly positioned ones. By perturbing endolysosomal membrane cholesterol levels, we show that dynein clustering directly depends on the amount of cholesterol on the endolysosomal membrane. Finally, we show that the dynein adapter protein ORP1L (Oxysterol Binding Protein Homologue) regulates dynein clustering and endolysosomal positioning through its cholesterol binding domain in response to membrane cholesterol levels.Competing Interest StatementThe authors have declared no competing interest.