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

TitleOpposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in Caenorhabditis elegans
Authors
KeywordsNeurite growth
Microtubules
Molecular chaperones
Ubiquitylation-proteasome system
Protein homeostasis
Issue Date2020
PublisherThe Company of Biologists Ltd. The Journal's web site is located at http://dev.biologists.org
Citation
Development, 2020, v. 147 n. 12, p. article no. dev189886 How to Cite?
AbstractMolecular 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.
Persistent Identifierhttp://hdl.handle.net/10722/284714
ISSN
2023 Impact Factor: 3.7
2023 SCImago Journal Rankings: 1.852
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZheng, C-
dc.contributor.authorAtlas, E-
dc.contributor.authorLee, HMT-
dc.contributor.authorJao, SLJ-
dc.contributor.authorNguyen, KCQ-
dc.contributor.authorHall, DH-
dc.contributor.authorChalfie, M-
dc.date.accessioned2020-08-07T09:01:40Z-
dc.date.available2020-08-07T09:01:40Z-
dc.date.issued2020-
dc.identifier.citationDevelopment, 2020, v. 147 n. 12, p. article no. dev189886-
dc.identifier.issn0950-1991-
dc.identifier.urihttp://hdl.handle.net/10722/284714-
dc.description.abstractMolecular 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.-
dc.languageeng-
dc.publisherThe Company of Biologists Ltd. The Journal's web site is located at http://dev.biologists.org-
dc.relation.ispartofDevelopment-
dc.subjectNeurite growth-
dc.subjectMicrotubules-
dc.subjectMolecular chaperones-
dc.subjectUbiquitylation-proteasome system-
dc.subjectProtein homeostasis-
dc.titleOpposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in Caenorhabditis elegans-
dc.typeArticle-
dc.identifier.emailZheng, C: cgzheng@hku.hk-
dc.identifier.emailLee, HMT: tlhm@hku.hk-
dc.identifier.authorityZheng, C=rp02473-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1242/dev.189886-
dc.identifier.pmid32467239-
dc.identifier.pmcidPMC7328132-
dc.identifier.scopuseid_2-s2.0-85086746522-
dc.identifier.hkuros312512-
dc.identifier.volume147-
dc.identifier.issue12-
dc.identifier.spagearticle no. dev189886-
dc.identifier.epagearticle no. dev189886-
dc.identifier.isiWOS:000567372300019-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl0950-1991-

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