Regulation of ER-phagy by a Ypt/Rab GTPase module |
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| Authors: | Zhanna Lipatova Ankur H Shah Jane J Kim Jonathan W Mulholland Nava Segev |
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| Institution: | University of Chicago;aDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60612;bDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60612;cCell Sciences Imaging Facility, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305 |
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| Abstract: | Accumulation 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. |
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