Expression of a Fragment of Ankyrin 2 Disrupts the Structure of the Axon Initial Segment and Causes Axonal Degeneration in Drosophila.
Mol Neurobiol
; 56(8): 5689-5700, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-30666562
ABSTRACT
Neurodegenerative stimuli are often associated with perturbation of the axon initial segment (AIS), but it remains unclear whether AIS disruption is causative for neurodegeneration or is a downstream step in disease progression. Here, we demonstrate that either of two separate, genetically parallel pathways that disrupt the AIS induce axonal degeneration and loss of neurons in the central brain of Drosophila. Expression of a portion of the C-terminal tail of the Ank2-L isoform of Ankyrin severely shortens the AIS in Drosophila mushroom body (MB) neurons, and this shortening occurs through a mechanism that is genetically separate from the previously described Cdk5α-dependent pathway of AIS regulation. Further, either manipulation triggers morphological degeneration of MB axons and is accompanied by neuron loss. Taken together, our results are consistent with the hypothesis that disruption of the AIS is causally related to degeneration of fly central brain neurons, and we suggest that similar mechanisms may contribute to neurodegeneration in mammals.
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Base de dados:
MEDLINE
Assunto principal:
Anquirinas
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Proteínas de Drosophila
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Drosophila melanogaster
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Segmento Inicial do Axônio
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Degeneração Neural
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article