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Regulation of autophagosome formation by Rho kinase

Mleczak, Andrzej and Millar, Sarah and Tooze, Sharon A and Olson, Michael F and Chan, Edmond Y W (2013) Regulation of autophagosome formation by Rho kinase. Cellular Signalling, 25 (1). pp. 1-11. ISSN 0898-6568

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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: Article
ID code: 41331
Notes: Copyright © 2012 Elsevier Inc. All rights reserved.
Keywords: ROCK, Rho kinase, autophagy, autophagosome, lysosome, Pharmacy and materia medica, Cell Biology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 03 Oct 2012 09:35
    Last modified: 27 Mar 2014 10:32
    URI: http://strathprints.strath.ac.uk/id/eprint/41331

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