Distinct isoforms of the RFX transcription factor DAF-19 regulate ciliogenesis and maintenance of synaptic activity.
Neurons form elaborate subcellular structures such as dendrites, axons, cilia, and synapses to receive signals from their environment and to transmit them to the respective target cells. In the worm Caenorhabditis elegans, lack of the RFX transcription factor DAF-19 leads to the absence of cilia normally found on 60 sensory neurons. We now describe and functionally characterize three different isoforms of DAF-19. The short isoform DAF-19C is specifically expressed in ciliated sensory neurons and sufficient to rescue all cilia-related phenotypes of daf-19 mutants. In contrast, the long isoforms DAF-19A/B function in basically all nonciliated neurons. We discovered behavioral and cellular phenotypes in daf-19 mutants that depend on the isoforms daf-19a/b. These novel synaptic maintenance phenotypes are reminiscent of synaptic decline seen in many human neurodegenerative disorders. The C. elegans daf-19 mutant worms can thus serve as a molecular model for the mechanisms of functional neuronal decline.
Department of Biosciences and Nutrition, Karolinska Institute, S-14157 Huddinge, Sweden.
Gabriele
G
Senti
Peter
P
Swoboda
D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002923:Cilia / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007978:Levamisole / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000969:Antinematodal Agents; D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D002800:Cholinesterase Inhibitors; C410596:DAF-19 protein, C elegans; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D000071701:Regulatory Factor X Transcription Factors; D050827:Syntaxin 1; D014157:Transcription Factors; C494215:unc-64 protein, C elegans; D007978:Levamisole; D000448:Aldicarb