Opposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in Caenorhabditis elegans.
Development
; 147(12)2020 06 17.
Article
em En
| MEDLINE
| ID: mdl-32467239
ABSTRACT
Molecular chaperones often work collaboratively with the ubiquitylation-proteasome system (UPS) to facilitate the degradation of misfolded proteins, which typically safeguards cellular differentiation and protects cells from stress. In this study, however, we report that the Hsp70/Hsp90 chaperone machinery and an F-box protein, MEC-15, have opposing effects on neuronal differentiation, and that the chaperones negatively regulate neuronal morphogenesis and functions. Using the touch receptor neurons (TRNs) of Caenorhabditis elegans, we find that mec-15(-) mutants display defects in microtubule formation, neurite growth, synaptic development and neuronal functions, and that these defects can be rescued by the loss of Hsp70/Hsp90 chaperones and co-chaperones. MEC-15 probably functions in a Skp-, Cullin- and F-box- containing complex to degrade DLK-1, which is an Hsp90 client protein stabilized by the chaperones. The abundance of DLK-1, and likely other Hsp90 substrates, is fine-tuned by the antagonism between MEC-15 and the chaperones; this antagonism regulates TRN development, as well as synaptic functions of GABAergic motor neurons. Therefore, a balance between the UPS and the chaperones tightly controls neuronal differentiation.
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Base de dados:
MEDLINE
Assunto principal:
Neuritos
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Caenorhabditis elegans
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Proteínas de Choque Térmico HSP90
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Proteínas de Caenorhabditis elegans
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Proteínas F-Box
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Microtúbulos
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article