RT Journal Article SR Electronic T1 Opposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in Caenorhabditis elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.13.944967 DO 10.1101/2020.02.13.944967 A1 Chaogu Zheng A1 Emily Atlas A1 Ho Ming Terence Lee A1 Susan Laura Javier Jao A1 Ken C. Q. Nguyen A1 David H. Hall A1 Martin Chalfie YR 2020 UL http://biorxiv.org/content/early/2020/05/05/2020.02.13.944967.abstract AB Molecular chaperones often work collaboratively with the ubiquitination-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 these defects can be rescued by the loss of Hsp70/Hsp90 chaperones and cochaperones. MEC-15 likely functions in a SCF 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 chaperones; this antagonism regulates TRN development as well as synaptic functions of GABAergic motor neurons. Therefore, a balance between UPS and chaperones tightly controls neuronal differentiation.Summary statement Molecular chaperones are known to protect cells from stress. However, in this study the authors showed that the Hsp90 chaperone negatively regulates neuronal differentiation when the ubiquitination-proteasome system is compromised.Competing Interest StatementThe authors have declared no competing interest.