scholarly journals Zonda is a novel early component of the autophagy pathway in Drosophila

2017 ◽  
Vol 28 (22) ◽  
pp. 3070-3081 ◽  
Author(s):  
Mariana Melani ◽  
Ayelén Valko ◽  
Nuria M. Romero ◽  
Milton O. Aguilera ◽  
Julieta M. Acevedo ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Kinase Domain ◽  
Eukaryotic Cells ◽  
Early Component ◽  
Early Stages ◽  
Autophagy Pathway ◽  
Phosphatidylinositol 3

Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel Drosophila immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediated phosphatidylinositol 3-phosphate (PI3P) deposition. Zonda displays an even distribution under basal conditions and, soon after starvation, nucleates in endoplasmic reticulum–associated foci that colocalize with omegasome markers. Zonda nucleation depends on Atg1, Atg13, and Atg17 but does not require Vps34, Vps15, Atg6, or Atg14. Zonda interacts physically with Atg1 through its kinase domain, as well as with Atg6 and Vps34. We propose that Zonda is an early component of the autophagy cascade necessary for Vps34-dependent PI3P deposition and omegasome formation.

scholarly journals Regulation of ER-phagy by a Ypt/Rab GTPase module

2013 ◽  
Vol 24 (19) ◽  
pp. 3133-3144 ◽  
Author(s):  
Zhanna Lipatova ◽  
Ankur H. Shah ◽  
Jane J. Kim ◽  
Jonathan W. Mulholland ◽  
Nava Segev
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Trafficking ◽  
Eukaryotic Cells ◽  
Rab Gtpase ◽  
Rab Gtpases ◽  
Cellular Compartment ◽  
Selective Autophagy ◽  
Downstream Effector ◽  
Golgi Transport ◽  
Autophagy Pathway

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.

Intramembrane proteolysis and post-targeting functions of signal peptides

2003 ◽  
Vol 31 (6) ◽  
pp. 1243-1247 ◽  
Author(s):  
B. Martoglio
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Bilayer ◽  
Signal Peptide ◽  
Eukaryotic Cells ◽  
Endoplasmic Reticulum Membrane ◽  
Signal Peptides ◽  
Peptide Fragments ◽  
Intramembrane Proteolysis ◽  
Signal Sequences ◽  
Membrane Spanning

Signal sequences are the addresses of proteins destined for secretion. In eukaryotic cells, they mediate targeting to the endoplasmic reticulum membrane and insertion into the translocon. Thereafter, signal sequences are cleaved from the pre-protein and liberated into the endoplasmic reticulum membrane. We have recently reported that some liberated signal peptides are further processed by the intramembrane-cleaving aspartic protease signal peptide peptidase. Cleavage in the membrane-spanning portion of the signal peptide promotes the release of signal peptide fragments from the lipid bilayer. Typical processes that include intramembrane proteolysis is the regulatory or signalling function of cleavage products. Likewise, signal peptide fragments liberated upon intramembrane cleavage may promote such post-targeting functions in the cell.

Orientation of the v-erb-B gene product in the plasma membrane

1986 ◽  
Vol 6 (4) ◽  
pp. 1329-1333
Author(s):  
R C Schatzman ◽  
G I Evan ◽  
M L Privalsky ◽  
J M Bishop
Keyword(s):  
Endoplasmic Reticulum ◽  
Epidermal Growth Factor Receptor ◽  
Plasma Membrane ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Amino Terminus ◽  
Protein Kinase Domain ◽  
Epidermal Growth

The retroviral oncogene v-erb-B encodes a truncated version of the receptor for epidermal growth factor. To define the disposition of the v-erb-B protein within cells and across the plasma membrane, we raised antibodies against defined epitopes in the protein and used these in immunofluorescence to analyze cells transformed by v-erb-B. A small fraction of the v-erb-B protein was found on the plasma membrane in a clustered configuration. The bulk of the protein was located in the endoplasmic reticulum and Golgi apparatus. Epitopes near the amino terminus of the v-erb-B protein were displayed on the surface of the cell, whereas epitopes in the protein kinase domain were located exclusively within cells. We conclude that the v-erb-B protein spans the plasma membrane in a manner similar or identical to that of the epidermal growth factor receptor, even though the viral transforming protein does not possess the signal peptide that is thought to direct insertion of the receptor into the membrane.

scholarly journals The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis

2019 ◽  
Vol 30 (9) ◽  
pp. 1069-1084 ◽  
Author(s):  
Danny Mollerup Sørensen ◽  
Henrik Waldal Holen ◽  
Jesper Torbøl Pedersen ◽  
Helle Juel Martens ◽  
Daniele Silvestro ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Marked Change ◽  
Hydrolytic Activity ◽  
Genetic Interactions ◽  
Eukaryotic Cells ◽  
Lipid Bodies ◽  
Increased Sensitivity ◽  
Phosphatidylinositol 4 ◽  
P Type

P5A ATPases are expressed in the endoplasmic reticulum (ER) of all eukaryotic cells, and their disruption results in severe ER stress. However, the function of these ubiquitous membrane proteins, which belong to the P-type ATPase superfamily, is unknown. We purified a functional tagged version of the Saccharomyces cerevisiae P5A ATPase Spf1p and observed that the ATP hydrolytic activity of the protein is stimulated by phosphatidylinositol 4-phosphate (PI4P). Furthermore, SPF1 exhibited negative genetic interactions with SAC1, encoding a PI4P phosphatase, and with OSH1 to OSH6, encoding Osh proteins, which, when energized by a PI4P gradient, drive export of sterols and lipids from the ER. Deletion of SPF1 resulted in increased sensitivity to inhibitors of sterol production, a marked change in the ergosterol/lanosterol ratio, accumulation of sterols in the plasma membrane, and cytosolic accumulation of lipid bodies. We propose that Spf1p maintains cellular sterol homeostasis by influencing the PI4P-induced and Osh-mediated export of sterols from the ER.

scholarly journals Phosphatidylinositol 3-Kinase/AKT Pathway Regulates the Endoplasmic Reticulum to Golgi Traffic of Ceramide in Glioma Cells

2008 ◽  
Vol 284 (8) ◽  
pp. 5088-5096 ◽  
Author(s):  
Paola Giussani ◽  
Loredana Brioschi ◽  
Rosaria Bassi ◽  
Laura Riboni ◽  
Paola Viani
Keyword(s):  
Endoplasmic Reticulum ◽  
Glioma Cells ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3
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