Expression of a human variant of CHMP2B linked to neurodegeneration in Drosophila external sensory organs leads to cell fate transformations associated with increased Notch activity
- 6 October 2019
- journal article
- research article
- Published by Wiley in Developmental Neurobiology
- Vol. 80 (3-4), 85-97
- https://doi.org/10.1002/dneu.22722
Abstract
Proper function of cell signaling pathways is dependent upon regulated membrane trafficking events that lead to the endocytosis, recycling, and degradation of cell surface receptors. The endosomal complexes required for transport (ESCRT) genes play a critical role in the sorting of ubiquitinated cell surface proteins. CHMP2BIntron5, a truncated form of a human ESCRT‐III protein, was discovered in a Danish family afflicted by a hereditary form of frontotemporal dementia (FTD). Although the mechanism by which the CHMP2B mutation in this family causes FTD is unknown, the resulting protein has been shown to disrupt normal endosomal–lysosomal pathway function and leads to aberrant regulation of signaling pathways. Here we have misexpressed CHMP2BIntron5 in the developing Drosophila external sensory (ES) organ lineage and demonstrate that it is capable of altering cell fates. Each of the cell fate transformations seen is compatible with an increase in Notch signaling. Furthermore, this interpretation is supported by evidence that expression of CHMP2BIntron5 in the notum environment is capable of raising the levels of Notch signaling. As such, these results add to a growing body of evidence that CHMP2BIntron5 can act rapidly to disrupt normal cellular function via the misregulation of critical cell surface receptor function.Keywords
Funding Information
- National Institute of General Medical Sciences (P20GM103423)
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