uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Three dimensional electron tomography characterization of islet amyloid polypeptide aggregates in drosophila melanogaster
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
2014 (English)In: Electron tomography, 2014Conference paper, Published paper (Refereed)
Abstract [en]

In human more than 30 different proteins can misfold and form amyloid. Alzheimer’s disease (AD) and type 2 diabetes (T2D) are common disease where amyloid deposits play an important role in the pathogenesis. In AD, amyloid beta precursor protein (AβPP) deposits in brain and in T2D form islet amyloid polypeptide (IAPP) amyloid in islets of langerhans that leads to destruction of the insulin producing beta cells. [1]

There are mouse and rat models that facilitate studies on AβPP and IAPP aggregation and subsequent development of respective disease, however, it is a long process that extend over many months. Therefore, we and others have established Drosophila melanogaster models that enable studies of amyloid protein misfolding and cellular effects [2].

Structural analysis on the misfolded protein aggregates provide data important for understanding the driving force of protein aggregation and how one protein can adopt different structures dependent on the biological environment. We have applied transmission electron microscopy (TEM) to study the structure of IAPP aggregates formed in Drosophila melanogaster. As shown in figure 1, we detected highly ordered IAPP aggregates in Drosophila melanogaster expressing human IAPP. However, from single 2D TEM image (as shown in figure 1), we are not able to determine the structural information in Z direction. Therefore, we have applied electron tomography technique to study the structural information in Z direction. The tilt series were acquired from 60 ̊ to -60 ̊, and double tilt series were carried out in order to minimize the elongation effect in Z direction. [3] The IMOD software was used for image alignment and reconstruction. [4]

In summary, IAPP aggregates detected in the drosophila melanogaster exhibit a spherical shape in the reconstructed tomogram, and spheres are arranged in a body center cubic structure. The individual spheres have a diameter of 17 nm and BCC structure is shown in figure 2 with a distance of 25 nm between.

References

[1] Sipe JD, et al., Amyloid, 2012,19:167

[2] Schultz SW, et al., PLoS One. 2011; 6(6): e20221

[3] Midgley PA, et al., Ultramicroscopy, 2003 96:413

[4] Mastronarde DN J Struct Biol, 1997,120:343

Place, publisher, year, edition, pages
2014.
Keyword [en]
Electron tomography
National Category
Natural Sciences Engineering and Technology
Identifiers
URN: urn:nbn:se:uu:diva-285829OAI: oai:DiVA.org:uu-285829DiVA: diva2:921195
Conference
18th International Microscopy Congress
Available from: 2016-04-19 Created: 2016-04-19 Last updated: 2016-08-12Bibliographically approved

Open Access in DiVA

No full text

Authority records BETA

Xie, LingGu, XiaohongWestermark, GunillaLeifer, Klaus

Search in DiVA

By author/editor
Xie, LingGu, XiaohongWestermark, GunillaLeifer, Klaus
By organisation
Applied Materials SciencesDepartment of Medical Cell Biology
Natural SciencesEngineering and Technology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 708 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf