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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
Author(s) -
Wilson Caroline,
Kavaler Joshua,
Ahmad Syed Tariq
Publication year - 2019
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.22722
Subject(s) - escrt , biology , endosome , microbiology and biotechnology , notch signaling pathway , cell fate determination , neurodegeneration , signal transduction , neuroscience , genetics , gene , transcription factor , intracellular , medicine , disease , pathology
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. CHMP2B Intron5 , 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 CHMP2B Intron5 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 CHMP2B Intron5 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 CHMP2B Intron5 can act rapidly to disrupt normal cellular function via the misregulation of critical cell surface receptor function.