Regulation of autophagosome formation by Rho kinase

Mleczak, A., Millar, S., Tooze, S.A., Olson, M.F. and Chan, E.Y.W. (2013) Regulation of autophagosome formation by Rho kinase. Cellular Signalling, 25(1), pp. 1-11. (doi: 10.1016/j.cellsig.2012.09.010)

Full text not currently available from Enlighten.

Abstract

Macroautophagy, commonly referred to as autophagy, is a protein degradation pathway that functions at a constitutive level in cells, which may become further activated by stressors such as nutrient starvation or protein aggregation. Autophagy has multiple beneficial roles for maintaining normal cellular homeostasis and these roles are related to the implications of autophagy in disease mechanisms including neurodegeneration and cancer. We previously searched for novel autophagy regulators and identified Rho-kinase 1 (ROCK1) as a candidate. Here, we show that activated ROCK1 inhibits autophagy in human embryonic kidney 293 cells. Conversely, ROCK inhibitory compounds enhanced the autophagy response to amino acid starvation or rapamycin treatment. Inhibition of ROCK during the starvation period led to a more rapid response with the production of larger early autophagosomes that matured into enlarged late degradative autolysosomes. Despite the production of enlarged LC3-positive early autophagosomes, membrane precursors containing WD-repeat protein interacting with phosphoinositides 1 (WIPI1) and mammalian Atg9 were not affected by ROCK inhibition, suggesting that phagophore elongation had been unusually extended. However, the enlarged autophagosomes were enriched in ULK1 which was essential to allow progression of autophagy flux. Our results demonstrate a novel role for ROCK in the control of autophagosome size and degradative capacity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Olson, Professor Michael
Authors: Mleczak, A., Millar, S., Tooze, S.A., Olson, M.F., and Chan, E.Y.W.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cellular Signalling
ISSN:0898-6568
Published Online:10 September 2012
Published Online:10 September 2012

University Staff: Request a correction | Enlighten Editors: Update this record