Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437

Nilay Nandi, Lauren K. Tyra, Drew Stenesen, Helmut Krämer

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Drosophila melanogaster Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels. The phospho-mimetic S437D mutation stabilizes Acn and promotes basal autophagy. In p35 mutants, basal autophagy and lifespan are reduced, but restored to near wild-type levels in the presence of stabilized AcnS437D. Expression of aggregation- prone polyQ-containing proteins or the Amyloid-β42 peptide, but not alpha-Synuclein, enhances Cdk5-dependent phosphorylation of S437-Acn. Our data indicate that Cdk5 is required to maintain the protective role of basal autophagy in the initial responses to a subset of neurodegenerative challenges.

Original languageEnglish (US)
Article numbere30760
JournaleLife
Volume6
DOIs
StatePublished - Dec 11 2017

Fingerprint

Phosphorylation
Autophagy
Drosophila melanogaster
alpha-Synuclein
Nuclear Proteins
Amyloid
Phosphotransferases
Agglomeration
Health
Peptides
Amyloidogenic Proteins
Starvation
Proteins
Mutation
polyglutamine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437 . / Nandi, Nilay; Tyra, Lauren K.; Stenesen, Drew; Krämer, Helmut.

In: eLife, Vol. 6, e30760, 11.12.2017.

Research output: Contribution to journalArticle

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