RT Journal Article
T1 mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1
A1 Kaeser Pebernard, Stéphanie
A1 Vionnet, Christine
A1 Mari, Muriel
A1 Sankar, Devanarayanan Siva
A1 Hu, Zehan
A1 Roubaty, Carole
A1 Martínez Martínez, Esther
A1 Zhao, Huiyuan
A1 Spuch Calvar, Miguel
A1 Petri Fink, Alke
A1 Rainer, Gregor
A1 Steinberg, Florian
A1 Reggiori, Fulvio
A1 Dengjel, Jörn
K1 2302 Bioquímica
K1 2410.07 Genética Humana
AB The protein kinase mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and proliferation, supporting anabolic reactions and inhibiting catabolic pathways like autophagy. Its hyperactivation is a frequent event in cancer promoting tumor cell proliferation. Several intracellular membrane-associated mTORC1 pools have been identified, linking its function to distinct subcellular localizations. Here, we characterize the N-terminal kinase-like protein SCYL1 as a Golgi-localized target through which mTORC1 controls organelle distribution and extracellular vesicle secretion in breast cancer cells. Under growth conditions, SCYL1 is phosphorylated by mTORC1 on Ser754, supporting Golgi localization. Upon mTORC1 inhibition, Ser754 dephosphorylation leads to SCYL1 displacement to endosomes. Peripheral, dephosphorylated SCYL1 causes Golgi enlargement, redistribution of early and late endosomes and increased extracellular vesicle release. Thus, the mTORC1-controlled phosphorylation status of SCYL1 is an important determinant regulating subcellular distribution and function of endolysosomal compartments. It may also explain the pathophysiology underlying human genetic diseases such as CALFAN syndrome, which is caused by loss-of-function of SCYL1.
PB Nature Communications
SN 20411723
YR 2022
FD 2022-08-10
LK http://hdl.handle.net/11093/4560
UL http://hdl.handle.net/11093/4560
LA eng
NO Nature Communications, 13(1): 4685 (2022)
NO Novo Nordisk Fonden | Ref. 0066384
DS Investigo
RD 11-sep-2024