Regulation of ER-phagy by a Ypt/Rab GTPase module.
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.
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60612 Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60612 Cell Sciences Imaging Facility, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305.
Zhanna
Z
Lipatova
Ankur H
AH
Shah
Jane J
JJ
Kim
Jonathan W
JW
Mulholland
Nava
N
Segev
D001343:Autophagy / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006056:Golgi Apparatus / Q000378:metabolism; D008247:Lysosomes; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport / Q000235:genetics; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C060755:YPT1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins