scholarly journals Regulation of Golgi turnover by CALCOCO1-mediated selective autophagy

2021 ◽  
Vol 220 (6) ◽  
Author(s):  
Thaddaeus Mutugi Nthiga ◽  
Birendra Kumar Shrestha ◽  
Jack-Ansgar Bruun ◽  
Kenneth Bowitz Larsen ◽  
Trond Lamark ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Golgi Complex ◽  
Eukaryotic Cells ◽  
Golgi Membrane ◽  
Selective Autophagy ◽  
Physiological Demands ◽  
Size And Morphology ◽  
In Cells

The Golgi complex is essential for the processing, sorting, and trafficking of newly synthesized proteins and lipids. Golgi turnover is regulated to meet different cellular physiological demands. The role of autophagy in the turnover of Golgi, however, has not been clarified. Here we show that CALCOCO1 binds the Golgi-resident palmitoyltransferase ZDHHC17 to facilitate Golgi degradation by autophagy during starvation. Depletion of CALCOCO1 in cells causes expansion of the Golgi and accumulation of its structural and membrane proteins. ZDHHC17 itself is degraded by autophagy together with other Golgi membrane proteins such as TMEM165. Taken together, our data suggest a model in which CALCOCO1 mediates selective Golgiphagy to control Golgi size and morphology in eukaryotic cells via its interaction with ZDHHC17.

scholarly journals Atg27 Is Required for Autophagy-dependent Cycling of Atg9

2007 ◽  
Vol 18 (2) ◽  
pp. 581-593 ◽  
Author(s):  
Wei-Lien Yen ◽  
Julie E. Legakis ◽  
Usha Nair ◽  
Daniel J. Klionsky
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Golgi Complex ◽  
Transmembrane Protein ◽  
Eukaryotic Cells ◽  
Vesicle Formation ◽  
Catabolic Pathway ◽  
Autophagosome Formation ◽  
Yeast Saccharomyces Cerevisiae ◽  
Double Membrane ◽  
Selective Autophagy

Autophagy is a catabolic pathway for the degradation of cytosolic proteins or organelles and is conserved among all eukaryotic cells. The hallmark of autophagy is the formation of double-membrane cytosolic vesicles, termed autophagosomes, which sequester cytoplasm; however, the mechanism of vesicle formation and the membrane source remain unclear. In the yeast Saccharomyces cerevisiae, selective autophagy mediates the delivery of specific cargos to the vacuole, the analog of the mammalian lysosome. The transmembrane protein Atg9 cycles between the mitochondria and the pre-autophagosomal structure, which is the site of autophagosome biogenesis. Atg9 is thought to mediate the delivery of membrane to the forming autophagosome. Here, we characterize a second transmembrane protein Atg27 that is required for specific autophagy in yeast. Atg27 is required for Atg9 cycling and shuttles between the pre-autophagosomal structure, mitochondria, and the Golgi complex. These data support a hypothesis that multiple membrane sources supply the lipids needed for autophagosome formation.

scholarly journals Assembly and disassembly of the Golgi complex: two processes arranged in a cis-trans direction.

1992 ◽  
Vol 116 (1) ◽  
pp. 69-83 ◽  
Author(s):  
J Alcalde ◽  
P Bonay ◽  
A Roa ◽  
S Vilaro ◽  
I V Sandoval
Keyword(s):  
Membrane Proteins ◽  
Golgi Complex ◽  
Rat Kidney ◽  
Brefeldin A ◽  
Golgi Membrane ◽  
Temperature Conditions ◽  
Selective Fusion ◽  
Normal Rat ◽  
Short Times

We have studied the disassembly and assembly of two morphologically and functionally distinct parts of the Golgi complex, the cis/middle and trans cisterna/trans network compartments. For this purpose we have followed the redistribution of three cis/middle- (GMPc-1, GMPc-2, MG 160) and two trans- (GMPt-1 and GMPt-2) Golgi membrane proteins during and after treatment of normal rat kidney (NRK) cells with brefeldin A (BFA). BFA induced complete disassembly of the cis/middle- and trans-Golgi complex and translocation of GMPc and GMPt to the ER. Cells treated for short times (3 min) with BFA showed extensive disorganization of both cis/middle- and trans-Golgi complexes. However, complete disorganization of the trans part required much longer incubations with the drug. Upon removal of BFA the Golgi complex was reassembled by a process consisting of three steps: (a) exist of cis/middle proteins from the ER and their accumulation into vesicular structures scattered throughout the cytoplasm; (b) gradual relocation and accumulation of the trans proteins in the vesicles containing the cis/middle proteins; and (c) assembly of the cisternae, and reconstruction of the Golgi complex within an area located in the vicinity of the centrosome from which the ER was excluded. Reconstruction of the cis/middle-Golgi complex occurred under temperature conditions inhibitory of the reorganization of the trans-Golgi complex, and was dependent on microtubules. Reconstruction of the trans-Golgi complex, disrupted with nocodazole after selective fusion of the cis/middle-Golgi complex with the ER, occurred after the release of cis/middle-Golgi proteins from the ER and the assembly of the cis/middle cisternae.

The role of the phosphoinositides at the Golgi complex

2007 ◽  
Vol 74 ◽  
pp. 107-116 ◽  
Author(s):  
Maria Antonietta De Matteis ◽  
Giovanni D'Angelo
Keyword(s):  
Golgi Complex ◽  
Small Gtpases ◽  
Eukaryotic Cells ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Cell Organelles ◽  
Binding Domains ◽  
Ability To Act ◽  
Endocytic Pathways

Eukaryotic cells are organized into a complex system of subcompartments, each with its distinct protein and lipid composition. A continuous flux of membranes crosses these compartments, and in some cases direct connections exist between the different organelles. It is thus surprising that they can maintain their individual identities. Small GTPases and the phosphoinositides have emerged as the key regulators in the maintenance of the identity of the Golgi complex. This property is due to their ability to act either alone or, more often, in combination, as cues directing and controlling the recruitment of proteins that possess phosphoinositide-binding domains. Among these many proteins there are the lipid transfer proteins, which can transfer ceramide, oxysterol, cholesterol and possibly glucosylceramide. By regulating these lipid transfer proteins in this way, this binomial combination of the small GTPases and the phosphoinositides acquires a further important role: control of the synthesis and/or distribution of other important integral constituents of cell organelles, such as the sphingolipids and cholesterol. This role is particularly relevant at the level of the Golgi complex, a key organelle in the biosynthesis, transport and sorting of both lipids and proteins that is located at the intersection of the secretory and endocytic pathways.

scholarly journals Selective Autophagy by Close Encounters of the Ubiquitin Kind

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2349 ◽  
Author(s):  
Anna Vainshtein ◽  
Paolo Grumati
Keyword(s):  
Protein Aggregates ◽  
Degradation Process ◽  
Eukaryotic Cells ◽  
Post Translational Modifications ◽  
Selective Autophagy ◽  
Close Encounters ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Cellular Turnover

Autophagy, a bulk degradation process within eukaryotic cells, is responsible for cellular turnover and nutrient liberation during starvation. Increasing evidence indicate that this process can be extremely discerning. Selective autophagy segregates and eliminates protein aggregates, damaged organelles, and invading organisms. The specificity of this process is largely mediated by post-translational modifications (PTMs), which are recognized by autophagy receptors. These receptors grant autophagy surgical precision in cargo selection, where only tagged substrates are engulfed within autophagosomes and delivered to the lysosome for proteolytic breakdown. A growing number of selective autophagy receptors have emerged including p62, NBR1, OPTN, NDP52, TAX1BP1, TOLLIP, and more continue to be uncovered. The most well-documented PTM is ubiquitination and selective autophagy receptors are equipped with a ubiquitin binding domain and an LC3 interacting region which allows them to physically bridge cargo to autophagosomes. Here, we review the role of ubiquitin and ubiquitin-like post-translational modifications in various types of selective autophagy.

scholarly journals Cholesterol-independent Targeting of Golgi Membrane Proteins in Insect Cells

1997 ◽  
Vol 8 (11) ◽  
pp. 2111-2118 ◽  
Author(s):  
Melissa M. Rolls ◽  
Marianne T. Marquardt ◽  
Margaret Kielian ◽  
Carolyn E. Machamer
Keyword(s):  
Membrane Proteins ◽  
Golgi Complex ◽  
Secretory Pathway ◽  
Protein Targeting ◽  
Insect Cells ◽  
Golgi Membrane ◽  
Cellular Cholesterol ◽  
Golgi Region ◽  
Intracellular Organelles ◽  
Aedes Albopictus Cells

Distinct lipid compositions of intracellular organelles could provide a physical basis for targeting of membrane proteins, particularly where transmembrane domains have been shown to play a role. We tested the possibility that cholesterol is required for targeting of membrane proteins to the Golgi complex. We used insect cells for our studies because they are cholesterol auxotrophs and can be depleted of cholesterol by growth in delipidated serum. We found that two well-characterized mammalian Golgi proteins were targeted to the Golgi region of Aedes albopictus cells, both in the presence and absence of cellular cholesterol. Our results imply that a cholesterol gradient through the secretory pathway is not required for membrane protein targeting to the Golgi complex, at least in insect cells.

scholarly journals Lysophosphatidic acid acyltransferase 3 regulates Golgi complex structure and function

2009 ◽  
Vol 186 (2) ◽  
pp. 211-218 ◽  
Author(s):  
John A. Schmidt ◽  
William J. Brown
Keyword(s):  
Lysophosphatidic Acid ◽  
Golgi Complex ◽  
Membrane Trafficking ◽  
Functional Organization ◽  
Complex Structure ◽  
Golgi Membrane ◽  
Direct Role ◽  
Tubule Formation ◽  
In Cells

Recent studies have suggested that the functional organization of the Golgi complex is dependent on phospholipid remodeling enzymes. Here, we report the identification of an integral membrane lysophosphatidic acid–specific acyltransferase, LPAAT3, which regulates Golgi membrane tubule formation, trafficking, and structure by altering phospholipids and lysophospholipids. Overexpression of LPAAT3 significantly inhibited the formation of Golgi membrane tubules in vivo and in vitro. Anterograde and retrograde protein trafficking was slower in cells overexpressing LPAAT3 and accelerated in cells with reduced expression (by siRNA). Golgi morphology was also dependent on LPAAT3 because its knockdown caused the Golgi to become fragmented. These data are the first to show a direct role for a specific phospholipid acyltransferase in regulating membrane trafficking and organelle structure.

scholarly journals Anterograde and retrograde traffic between the rough endoplasmic reticulum and the Golgi complex.

1995 ◽  
Vol 131 (6) ◽  
pp. 1387-1401 ◽  
Author(s):  
J C Stinchcombe ◽  
H Nomoto ◽  
D F Cutler ◽  
C R Hopkins
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Rough Endoplasmic Reticulum ◽  
Golgi Complex ◽  
Temperature Shift ◽  
Golgi Stack ◽  
Retrograde Traffic ◽  
Almost All ◽  
Golgi Network ◽  
In Cells

The transfer of newly synthesized membrane proteins moving from the rough endoplasmic reticulum (RER) to the Golgi complex has been studied by electron microscopy in HEp-2 cells transfected with cDNAs for chimeric proteins. These proteins consist of a reporter enzyme, horseradish peroxidase (HRP), anchored to the transmembrane domains of two integral membrane proteins, the transferrin receptor and sialyl-transferase. The chimeras are distributed throughout the nuclear envelope, RER, vesicular tubular clusters (VTCs) and a network of tubules in the cis-Golgi area. At 20 degrees C tubules containing chimera connect the RER to the VTCs and to the cis-Golgi network. On transfer to 37 degrees C in the presence of dithiothreitol (DTT), the chimeras are seen to move from the RER and through the Golgi stack. With this temperature shift the direct connections with the RER are lost and free vesicles form; some of these vesicles contain HRP reaction product which is much more concentrated than in the adjacent RER while others lack reaction product entirely. In cells expressing SSHRPKDEL, DAB reaction product remains distributed throughout the RER, the VTCs, and the cis-Golgi network for prolonged periods in the presence of DTT and almost all of the vesicles which form at 37 degrees C are DAB-positive. Together these observations demonstrate that all three chimeras are transported from the RER to the cis-Golgi in free, 40-60-nm vesicles at 37 degrees C. They also suggest that the retrograde traffic which carries SSHRPKDEL back to the RER is probably mediated by vesicles with a similar morphology but which, in cells expressing membrane-anchored chimeras, lack detectable reaction product.

A group of integral membrane proteins of the rat liver Golgi contains a conserved protein of 100 kDa

1994 ◽  
Vol 107 (12) ◽  
pp. 3425-3436
Author(s):  
J.G. Pryde
Keyword(s):  
Membrane Proteins ◽  
Rat Liver ◽  
Golgi Complex ◽  
Immunofluorescence Microscopy ◽  
Mammalian Species ◽  
Polyclonal Antiserum ◽  
Integral Membrane Proteins ◽  
Golgi Membrane ◽  
Wide Range ◽  
Triton X

Rat liver Golgi membranes were washed with KCl and urea, and a polyclonal antiserum that stained the Golgi complex by immunofluorescence microscopy was raised. A group of proteins of apparent molecular mass 500 kDa, 200 kDa and 100 kDa were identified by immunoblotting with the antiserum, and were enriched in the Golgi membrane fraction. These proteins were also localised to the Golgi by immunofluorescence microscopy with affinity-purified antibodies. They are integral membrane proteins, and protease digestion experiments suggested that they are not exposed on the cytoplasmic face of the Golgi membrane. Immunofluorescence microscopy showed that staining of the Golgi complex by antibodies to the 100 kDa Golgi protein can be demonstrated among a wide range of mammalian species. This conservation may point to an important structural or functional role for the molecule. When the 100 kDa protein was reduced with dithiothreitol it was no longer recognised by the anti-Golgi antiserum. During phase separation in Triton X-114 the 100 kDa protein partitioned into the aqueous phase, rather than into the detergent phase, suggesting that it has a large luminal domain of hydrophilic amino acids.

High Mobility Group Box-1 (HMGB1): A Potential Target in Therapeutics

2019 ◽  
Vol 20 (14) ◽  
pp. 1474-1485 ◽  
Author(s):  
Eyaldeva C. Vijayakumar ◽  
Lokesh Kumar Bhatt ◽  
Kedar S. Prabhavalkar
Keyword(s):  
Myocardial Infarction ◽  
Vagus Nerve Stimulation ◽  
Nuclear Protein ◽  
Therapeutic Potential ◽  
High Mobility ◽  
Dna Binding Protein ◽  
High Mobility Group ◽  
Eukaryotic Cells ◽  
Hmgb1 Protein

High mobility group box-1 (HMGB1) mainly belongs to the non-histone DNA-binding protein. It has been studied as a nuclear protein that is present in eukaryotic cells. From the HMG family, HMGB1 protein has been focused particularly for its pivotal role in several pathologies. HMGB-1 is considered as an essential facilitator in diseases such as sepsis, collagen disease, atherosclerosis, cancers, arthritis, acute lung injury, epilepsy, myocardial infarction, and local and systemic inflammation. Modulation of HMGB1 levels in the human body provides a way in the management of these diseases. Various strategies, such as HMGB1-receptor antagonists, inhibitors of its signalling pathway, antibodies, RNA inhibitors, vagus nerve stimulation etc. have been used to inhibit expression, release or activity of HMGB1. This review encompasses the role of HMGB1 in various pathologies and discusses its therapeutic potential in these pathologies.

scholarly journals Lipid Transporters Beam Signals from Cell Membranes

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 562
Author(s):  
Miliça Ristovski ◽  
Danny Farhat ◽  
Shelly Ellaine M. Bancud ◽  
Jyh-Yeuan Lee
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayers ◽  
Lipid Composition ◽  
Structural Integrity ◽  
Current Knowledge ◽  
Integral Membrane Proteins ◽  
Cellular Membranes ◽  
Cytoplasmic Proteins ◽  
Lipid Transporters

Lipid composition in cellular membranes plays an important role in maintaining the structural integrity of cells and in regulating cellular signaling that controls functions of both membrane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transporters, two integral membrane proteins, are known to contribute to lipid translocation across the lipid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membranes in regulating cell signaling and how lipid transporters participate this process.

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