Mol. Biol. Cell-2013-Lipatova-3133-44.pdf (1.97 MB)
Regulation of ER-phagy by a Ypt/Rab GTPase module
journal contribution
posted on 2014-02-19, 00:00 authored by Zhanna Lipatova, Ankur H. Shah, Jane J. Kim, Jonathan W. Mulholland, Nava SegevAccumulation of misfolded proteins on intracellular membranes has been implicated
in neurodegenerative diseases. One cellular pathway that clears such aggregates is endoplasmic reticulum autophagy (ER-phagy), a selective autophagy pathway that delivers
excess ER to the lysosome for degradation. Not much is known about the regulation of ER-phagy. The conserved Ypt/Rab GTPases regulate all membrane trafficking events in eukaryotic cells. We recently showed that a Ypt module, consisting of Ypt1 and autophagy-specific upstream activator and downstream effector, regulates the onset of selective autophagy
in yeast. Here we show that this module acts at the ER. Autophagy-specific mutations
in its components cause accumulation of excess membrane proteins on aberrant ER structures and induction of ER stress. This accumulation is due to a block in transport of these membranes to the lysosome, where they are normally cleared. These findings establish
a role for an autophagy-specific Ypt1 module in the regulation of ER-phagy. Moreover, because Ypt1 is a known key regulator of ER-to-Golgi transport, these findings establish a second role for Ypt1 at the ER. We therefore propose that individual Ypt/Rabs, in the context
of distinct modules, can coordinate alternative trafficking steps from one cellular compartment to different destinations.
Funding
This research was supported by National Institutes of Health Grant GM-45444 to N.S.
History
Publisher Statement
© 2013 Lipatova et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). This is a copy of an article published in the Molecular Biology of the Cell © 2013 American Society for Cell Biology. The published version is available at http://www.molbiolcell.org/Publisher
American Society for Cell BiologyLanguage
- en_US
issn
1939-4586Issue date
2013-10-01Usage metrics
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