Search: onr:"swepub:oai:research.chalmers.se:8d6537c1-43dd-44b5-bcaa-091ac858ef76" >
Role of Membrane Te...
Role of Membrane Tension Sensitive Endocytosis and Rho GTPases in the Uptake of the Alzheimer's Disease Peptide Aβ(1-42)
-
- Vilhelmsson Wesén, Emelie, 1989 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
- Lundmark, Richard (author)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Umeå University
-
- Esbjörner Winters, Elin, 1978 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
show more...
-
Esbjörner, Elin K. (author)
-
show less...
-
(creator_code:org_t)
- 2020-06-04
- 2020
- English.
-
In: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 11:13, s. 1925-1936
- Related links:
-
https://research.cha... (primary) (free)
-
show more...
-
https://pubs.acs.org...
-
https://doi.org/10.1...
-
https://research.cha...
-
https://research.cha...
-
https://urn.kb.se/re...
-
show less...
Abstract
Subject headings
Close
- Intraneuronal accumulation of amyloid-β (Aβ) is an early pathological signum of Alzheimer's disease, and compartments of the endolysosomal system have been implicated in both seeding and cell-cell propagation of Aβ aggregation. We have studied how clathrin-independent mechanisms contribute to Aβ endocytosis, exploring pathways that are sensitive to changes in membrane tension and the regulation of Rho GTPases. Using live cell confocal microscopy and flow cytometry, we show the uptake of monomeric Aβ(1-42) into endocytic vesicles and vacuole-like dilations, following relaxation of osmotic pressure-induced cell membrane tension. This indicates Aβ(1-42) uptake via clathrin independent carriers (CLICs), although overexpression of the bar-domain protein GRAF1, a key regulator of CLICs, had no apparent effect. We furthermore report reduced Aβ(1-42) uptake following overexpression of constitutively active forms of the Rho GTPases Cdc42 and RhoA, whereas modulation of Rac1, which is linked to macropinosome formation, had no effect. Our results confirm that uptake of Aβ(1-42) is clathrin-and dynamin-independent and point to the involvement of a new and distinct clathrin-independent endocytic mechanism which is similar to uptake via CLICs or macropinocytosis but that also appear to involve yet uncharacterized molecular players.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- uptake mechanism
- Aβ(1-42)
- cellular uptake
- clathrin-independent endocytosis (CIE)
- Alzheimer's disease
- Amyloid-β
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database