2014 Group 1 Project
- 1 Endocytosis
- 1.1 CLIC/GEEC endocytic pathway
- 1.2 Clathrin- and Dynamin-Independent Endocytosis of FGFR3 – Implications for Signalling
- 1.3 E3 ubiquitin ligase Pub1 is implicated in endocytosis of a GPI-anchored protein Ecm33 in fission yeast.
- 1.4 arf6-dependent endocytosis
- 1.5 Endocytosis of hERG Is Clathrin-Independent and Involves Arf6
- 1.6 ARF6-Dependent Regulation of P2Y Receptor Traffic and Function in Human Platelets
- 1.7 flotillin-dependent endocytosis
- 1.8 macropinocytosis
- 1.9 circular doral ruffles
- 1.10 phagocytosis
- 1.11 trans-endocytosis
- 2 Reference
- 3 Copyright
CLIC/GEEC endocytic pathway
Clathrin- and Dynamin-Independent Endocytosis of FGFR3 – Implications for Signalling
This article confirmed that the best studied endocytic mechanism is characterised by the formation of clarithin (a protein) coated pits at the plasma membrane. Epidermal Growth Factor Receptors (EGFR’s) that were internalised via a clarithin-mediated pathway were found to recycle back to the cell surface whereas EGFR’s that were internalised via a clarithin-independant pathway were degraded. This concluded that different endocytic pathways dictate further signalling and intracellular trafficking of their cargo.
The article is relevant because it categorised the CLIC/GEEC pathway as a clarithin-independant endocytic pathway. The article raised my awareness of the lack of information on this specific pathway. Even though many derivatives of clarithin-inependant endocytosis have been established, they are yet to be given definitive features in order to be repeatedly categorised. Therefore, further research into the subtypes of clarithin-independant pathways may prove difficult.
E3 ubiquitin ligase Pub1 is implicated in endocytosis of a GPI-anchored protein Ecm33 in fission yeast.
This study demonstrated that a GPI-anchored protein, Ecm33 is endocytosed in a Pub-1 dependant manner that is also required for the trafficking of non-GPI-anchored proteins in fission yeast. Ecm33 is important for cell wall integrity and function. Ubiquitylation was also studied but results were inconclusive in determining whether it is required for internalisation of GPI-anchored proteins. It was found however that when GPI-anchored proteins were endocytosed the main fraction of them were delivered to GEEC’s.
This article was of relevance because it defined GEEC as the acronym for GPI-anchored enriched endosomal compartment. This pathway seems to be specific for a type of protein on the cell membrane surface. Due to the similarities amongst yeast and mammalian cells, this study also provides a basis for further research into understanding the precise mechanism of endocytosis of GPI-anchored proteins in higher eukaryotes.
Endocytosis of hERG Is Clathrin-Independent and Involves Arf6
hERG potassium channels are important for repolarisation of the cardiac action potential. Reduced levels of expression increases the risk of ventricular arrhytmias. The results of this study found that this channel undergoes rapid internalisation which is neither inhibited by dynamin (an inhibitor of dynasore) nor Rab5a. This suggests the endocytosis of hERG is a clarithin-independant mechanism. A GTPase deficient mutant, Arf6-Q67L was compared and contrasted on two types of cells, HeLa and H9c2. Both of these had hERG channels present on the characteristic vacuole, concluding that Arf-6 is required for endocytosis of hERG potassium channels.
This article is relevant to the subtype of Arf-6 dependant endocytosis because it explores the clinical significance when this subtype is potentially malfunctioning. It demonstrates how different cells use different signalling mechanisms for endocytosis and how this variation can effect organs at the multicellular level.
ARF6-Dependent Regulation of P2Y Receptor Traffic and Function in Human Platelets
Arf-6 proteins were found to regulate intracellular trafficking by shuffling between an active GTP-bound form and an inactive GDP-bound form. A low level of Arf-6 GTP is essential for platelet aggregation and this was deduced to be regulated depending on platelet activation by collagen. when platelets are activated, the GTP-bound form of Arf-6 rapidly converts to its GDP-bound form. Arf-6 activity was also found to be stimulated by activation of P2Y purinoreceptors. These findings deduced that Arf-6 is a regulator of platelet function by demonstrating it has a function in internalisation of P2Y purinreceptors which in turn have an effect on platelet ADP receptor function.
This article shed some light on the Arf-6 dependant pathway of endocytosis. It is clear that Arf-6 is a type of kinase signal, controlling the level of endocytosis. Seeing as this endocytic pathway is common in human platelets, it may have close associations in haemolytic pathology and this may be an interesting avenue to investigate as part of the project.
circular doral ruffles
Localization of insulin receptor and caveolin-1 in endosomes by immuno-gold electron microscopy. Isolated adipocytes were incubated with insulin at 100 nM for 10 min. Cells were then homogenized and the endosomal fraction isolated. Endosome vesicles were attached to grids, immunogold-labeled against caveolin-1 (6 nm gold particles) and the insulin receptor (15 nm gold particles), lyophilized and sputtered with a 2-nm tungsten film before examination by transmission electron microscopy. C and D are blow-ups from B; arrowheads indicate patches of caveolin-1 labeling; arrows indicate insulin receptor labeling. One experiment of three with similar results is illustrated. doi:10.1371/journal.pone.0005985.g004
<pubmed>19543529</pubmed> | PLOS One
© 2009 Fagerholm et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Note - This image was originally uploaded as part of a student project and may contain inaccuracies in either description or acknowledgements. Please contact the site coordinator if the uploaded content does not meet the original copyright permission or requirements, for immediate removal.
Image showing effects of dynamin on FGF1 internalisation.
Figure 3: The effect of dynamin 1, dynamin 1 K44A, dynamin 2 or dynamin 2 K44A expression on FGF1 internalization. U2OS cells stably transfected with FGFR1 (A) or FGFR3 (B) were transfected with HA-tagged dynamin constructs as indicated and incubated with Cy3-FGF1 and 50 U/ml heparin at 37°C for 20 min. The cells were then fixed and stained with anti-HA antibody. The cells were examined with confocal microscopy. Bar, 5 µm. doi:10.1371/journal.pone.0021708.g003
© 2011 Haugsten et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Image of Uptake of MIF via CPZ sensitive endocytosis
© 2011 Xie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.