Mechanisms of Lipid Sorting in the Endosomal Pathway

2018 ◽  
pp. 1-39
Author(s):  
Bianca M. Esch ◽  
Florian Fröhlich
Keyword(s):  
Lipid Sorting ◽  
Endosomal Pathway

scholarly journals Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol

2021 ◽  
Author(s):  
Juan Carlos Polanco ◽  
Gabriel Rhys Hand ◽  
Adam Briner ◽  
Chuanzhou Li ◽  
Jürgen Götz
Keyword(s):  
Critical Role ◽  
Membrane Integrity ◽  
Lysosomal Degradation ◽  
Escape Route ◽  
Cellular Invasion ◽  
Endosomal Membrane ◽  
Late Endosomes ◽  
Endosomal Membranes ◽  
Endosomal Pathway ◽  
Tau Aggregation

AbstractThe microtubule-associated protein tau has a critical role in Alzheimer’s disease and other tauopathies. A proposed pathomechanism in the progression of tauopathies is the trans-synaptic spreading of tau seeds, with a role for exosomes which are secretory nanovesicles generated by late endosomes. Our previous work demonstrated that brain-derived exosomes isolated from tau transgenic rTg4510 mice encapsulate tau seeds with the ability to induce tau aggregation in recipient cells. We had also shown that exosomes can hijack the endosomal pathway to spread through interconnected neurons. Here, we reveal how tau seeds contained within internalized exosomes exploit mechanisms of lysosomal degradation to escape the endosome and induce tau aggregation in the cytosol of HEK293T-derived ‘tau biosensor cells’. We found that the majority of the exosome-containing endosomes fused with lysosomes to form endolysosomes. Exosomes induced their permeabilization, irrespective of the presence of tau seeds, or whether the exosomal preparations originated from mouse brains or HEK293T cells. We also found that permeabilization is a conserved mechanism, operating in both non-neuronal tau biosensor cells and primary neurons. However, permeabilization of endolysosomes only occurred in a small fraction of cells, which supports the notion that permeabilization occurs by a thresholded mechanism. Interestingly, tau aggregation was only induced in cells that exhibited permeabilization, presenting this as an escape route of exosomal tau seeds into the cytosol. Overexpression of RAB7, which is required for the formation of endolysosomes, strongly increased tau aggregation. Conversely, inhibition of lysosomal function with alkalinizing agents, or by knocking-down RAB7, decreased tau aggregation. Together, we conclude that the enzymatic activities of lysosomes permeabilize exosomal and endosomal membranes, thereby facilitating access of exosomal tau seeds to cytosolic tau to induce its aggregation. Our data underscore the importance of endosomal membrane integrity in mechanisms of cellular invasion by misfolded proteins that are resistant to lysosomal degradation.

Lipid sorting and clustering

2009 ◽  
Vol 10 (7) ◽  
pp. 442-443 ◽  
Author(s):  
Alicia Chung
Keyword(s):  
Lipid Sorting

scholarly journals Trafficking of prion proteins through a caveolae-mediated endosomal pathway

2003 ◽  
Vol 162 (4) ◽  
pp. 703-717 ◽  
Author(s):  
Peter J. Peters ◽  
Alexander Mironov ◽  
David Peretz ◽  
Elly van Donselaar ◽  
Estelle Leclerc ◽  
...  
Keyword(s):  
Prion Proteins ◽  
Protein A ◽  
Subcellular Location ◽  
Cellular Prion Protein ◽  
Endocytic Pathway ◽  
Live Cells ◽  
Trafficking Pathway ◽  
Late Endosomes ◽  
Endosomal Pathway ◽  
Glycosylphosphatidyl Inositol

To understand the posttranslational conversion of the cellular prion protein (PrPC) to its pathologic conformation, it is important to define the intracellular trafficking pathway of PrPC within the endomembrane system. We studied the localization and internalization of PrPC in CHO cells using cryoimmunogold electron microscopy. At steady state, PrPC was enriched in caveolae both at the TGN and plasma membrane and in interconnecting chains of endocytic caveolae. Protein A–gold particles bound specifically to PrPC on live cells. These complexes were delivered via caveolae to the pericentriolar region and via nonclassical, caveolae-containing early endocytic structures to late endosomes/lysosomes, thereby bypassing the internalization pathway mediated by clathrin-coated vesicles. Endocytosed PrPC-containing caveolae were not directed to the ER and Golgi complex. Uptake of caveolae and degradation of PrPC was slow and sensitive to filipin. This caveolae-dependent endocytic pathway was not observed for several other glycosylphosphatidyl inositol (GPI)-anchored proteins. We propose that this nonclassical endocytic pathway is likely to determine the subcellular location of PrPC conversion.

scholarly journals Pallidin is a novel interacting protein for cytohesin-2 and regulates the early endosomal pathway and dendritic formation in neurons

2018 ◽  
Vol 147 (2) ◽  
pp. 153-177 ◽  
Author(s):  
Akiko Ito ◽  
Masahiro Fukaya ◽  
Shintaro Saegusa ◽  
Emi Kobayashi ◽  
Takeyuki Sugawara ◽  
...  
Keyword(s):  
Interacting Protein ◽  
Endosomal Pathway

scholarly journals Interference with the endosomal acidification by a monoclonal antibody directed toward the 116 (100)-kD subunit of the vacuolar type proton pump.

1994 ◽  
Vol 127 (1) ◽  
pp. 39-53 ◽  
Author(s):  
S B Sato ◽  
S Toyama
Keyword(s):  
Monoclonal Antibody ◽  
Acridine Orange ◽  
Proton Pump ◽  
Viral Fusion ◽  
Enveloped Viruses ◽  
Human Osteosarcoma Cells ◽  
Endosomal Acidification ◽  
Membrane Compartments ◽  
Endosomal Pathway

A monoclonal antibody (OSW2) was prepared by using human osteosarcoma cells. OSW2 was found to be directed toward the 116 (also called 100)- kD protein that uniquely associates to the vacuolar-type proton pump. The antibody specifically localized acidic membrane compartments that could be visualized with acridine orange in many types of human cells. It also reacted with the surface and was internalized along the endosomal pathway. Monitoring the endosome pH by using FITC-dextran and acridine orange suggested that the antibody interfered with low pH. Cell-free experiments indicated that the ATP-dependent acidification was inhibited in endosomes associated with OSW2. In contrast, the antibody gave little effect on the ATPase activity of the solubilized H+ pump. The internalization of OSW2 reduced infectivity of certain enveloped viruses (influenza, SFV, VSV) by 50 to 80%. Inhibition of viral fusion was directly demonstrated by monitoring the fate of octadecylrhodamine-labeled influenza virus fluorescence. These results indicate that the 116 (100)-kD protein is necessary for the control of pH. The antibody represents a novel probe for understanding the role of the endosomal compartments in cellular physiology.

VEGF receptor trafficking in angiogenesis

2009 ◽  
Vol 37 (6) ◽  
pp. 1184-1188 ◽  
Author(s):  
Alice Scott ◽  
Harry Mellor
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Intracellular Trafficking ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Signalling Pathways ◽  
Vegf Receptor ◽  
A Cell ◽  
Endosomal Pathway

The intracellular trafficking of receptors provides a way to control the overall sensitivity of a cell to receptor stimulation. These sorting pathways are also used to shape the balance of signals that are generated in response to receptor activation. The major pro-angiogenic growth factor receptor is VEGFR2 (vascular endothelial growth factor 2). VEGFR2 activates a very similar set of signalling pathways to other RTKs (receptor tyrosine kinases); however, its intracellular trafficking is very different. Furthermore, VEGFR2 can form a complex with a range of different angiogenic regulators that in turn regulate the trafficking of VEGFR2 through the endosomal pathway. This regulated trafficking of VEGFR2 has important consequences for angiogenic signalling and is a clear demonstration of how the endosomal pathway plays a critical role in connecting receptor signalling pathways to cellular events.

scholarly journals Differential Endocytic Functions ofTrypanosoma bruceiRab5 Isoforms Reveal a Glycosylphosphatidylinositol-specific Endosomal Pathway

2001 ◽  
Vol 277 (11) ◽  
pp. 9529-9539 ◽  
Author(s):  
Arun Pal ◽  
Belinda S. Hall ◽  
Darren N. Nesbeth ◽  
Helen I. Field ◽  
Mark C. Field
Keyword(s):  
Endosomal Pathway
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