Opposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in Caenorhabditis elegans

Chaogu Zheng, Emily Atlas, Ho Ming Terence Lee, Susan Laura Javier Jao, Ken C.Q. Nguyen, David H. Hall, Martin Chalfie

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article numberdev189886
JournalDevelopment (Cambridge)
Volume147
Issue number12
DOIs
StatePublished - Jun 17 2020

Keywords

  • Microtubules
  • Molecular chaperones
  • Neurite growth
  • Protein homeostasis
  • Touch receptor neurons
  • Ubiquitylation-proteasome system

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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