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PMID:24465508

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Citation

Bitsikas, V, Riento, K, Howe, JD, Barry, NP and Nichols, BJ (2014) The role of flotillins in regulating aβ production, investigated using flotillin 1-/-, flotillin 2-/- double knockout mice. PLoS ONE 9:e85217

Abstract

Flotillin 1 and flotillin 2 associate in the plasma membrane to form microdomains that have roles in cell signaling, regulation of cell-cell contacts, membrane-cytoskeletal interactions, and endocytosis. They are thought to be involved in the trafficking and hence processing of the Amyloid Precursor Protein, APP. In this study we set out to obtain in vivo confirmation of a link between flotillins and cleavage of APP to release amyloidogenic Aβ peptide, and to generate tools that would allow us to ask whether flotillins are functionally redundant. We used a mouse model for Aβ-dependent cerebral amyloidosis, APPPS1 mice, combined with deletion of either flotillin 1 singly, or flotillin 1 and flotillin 2 together. There was a small but significant reduction in Aβ levels, and the abundance of congo-red stained plaques, in brains of 12 week old mice lacking flotillin 1. A similar reduction in Aβ levels was observed in the flotillin 1-/-, flotillin 2-/- double knockouts. We did not observe large effects on the clustering or endocytosis of APP in flotillin 1-/- mouse embryonic fibroblasts. We conclude that flotillins are likely to play some role in APP trafficking or processing, but the relevant cellular mechanisms require more investigation. The availability of flotillin 1-/-, flotillin 2-/- mice, which have no overt phenotypes, will facilitate research into flotillin function in vivo.

Links

PubMed PMC3897416 Online version:10.1371/journal.pone.0085217

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FLOT1

GO:0071806: beta-amyloid formation

ECO:0000315:

P

Figure 1: flow cytometry of knockout cells show decreased APP endocytosis.

complete
CACAO 9407

See also

References

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