University of Groningen
Polarized protein trafficking and disease
Overeem, Arend Wouter
DOI:
10.33612/diss.112660241
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Publication date:
2020
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Overeem, A. W. (2020). Polarized protein trafficking and disease: Towards understanding the traffic jams in
microvillus inclusion- and Wilson disease. Rijksuniversiteit Groningen.
https://doi.org/10.33612/diss.112660241
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Stellingen behorend bij het proefschrift:
Polarized protein trafficking and disease:
Towards understanding the traffic jams in Microvillus
In-clusion- and Wilson Disease.
Arend Overeem
1. Myosin Vb is not required for polarity establishment and apical targeting of trans-membrane proteins in hepatocytes.
2. The pathophysiological mechanisms of intestinal and liver symptoms in microvillus inclusion disease are inherently different. The former is dependent on a lack of myosin
Vb, while the latter is dependent on the presence of mutant myosin Vb.
3. Myosin Vb tail domain overexpression is not a good model for myosin Vb deficiency. Its use as such has led to an overestimation of the importance of myosin Vb in trafficking
of certain proteins.
4. The common H1069Q ATP7B mutation in Wilson disease patients is able to reach the Golgi apparatus of hepatocytes, in contrast with previous claims that is fully retained in
the ER.
5. We need to reconsider whether therapeutic strategies that target ER degradation are useful in Wilson disease, since decreasing ER degradation will not remove the second trafficking blockade: the impaired translocation of mutant ATP7B to the plasma
mem-brane.
6. Investigating the behavior of endogenous mutant proteins is superior to using overex-pression constructs, and future research should aim to use the former method if possible. 7. Differentiation of hepatocytes from iPS is an inherently complex process yielding var-iable mixtures of cell types. It will take many subsequent steps of purification and safety
testing before they can be used therapeutically.
8. Differentiation of cells on a flat culture surface is a poor, two-dimensional approxima-tion of a three-dimensional in utero developmental process. Developmental studies us-ing stem cells in vitro should strive to use 3-dimensional culture in the future if possible.
9. Science is as much rolling the dice, as it is hard work and cleverness.
10. The culture of iPS cells is unfortunately not very compatible with recreational week-end activities.
