Control of Nonapoptotic Developmental Cell Death in Caenorhabditis elegans by a Polyglutamine-Repeat Protein

• Published in: Science (American Association for the Advancement of Science) 2012-02, Vol.335 (6071), p.970-973
• Main Authors: Blum, Elyse S., Abraham, Mary C., Yoshimura, Satoshi, Lu, Yun, Shaham, Shai
• Format: Article
• Language: English
• Subjects: Alleles; Amino Acid Motifs; Amino Acid Sequence; Animals; Apoptosis; Biological and medical sciences; Caenorhabditis elegans - cytology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell aggregates; Cell Death; Cell nucleus; Cell Nucleus - ultrastructure; Cell Survival; Classical genetics, quantitative genetics, hybrids; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes, Helminth; Genetic screening; Genetics of eukaryotes. Biological and molecular evolution; Genome, Helminth; Invertebrata; Male; Male animals; MAP Kinase Kinase 4 - genetics; MAP Kinase Kinase 4 - metabolism; Molecular Sequence Data; Mutant Proteins - chemistry; Mutant Proteins - metabolism; Neurons; Nuclear membrane; Peptides - chemistry; Protein Structure, Tertiary; RNA Interference; Sequence Deletion; Swelling; Transcription Factors - genetics; Transcription Factors - metabolism; Transgenes; Vertebrates
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1215156

Death is a vital developmental cell fate. In Caenorhabditis elegans, programmed death of the linker cell, which leads gonadal elongation, proceeds independently of caspases and apoptotic effectors. To identify genes promoting linker-cell death, we performed a genome-wide RNA interference screen. We show that linker-cell death requires the gene pqn-41, encoding an endogenous polyglutamine-repeat protein, pqn-41 functions cell-autonomously and is expressed at the onset of linker-cell death, pqn-41 expression is controlled by the mitogen-activated protein kinase kinase SEK-1, which functions in parallel to the zinc-finger protein LIN-29 to promote cellular demise. Linker-cell death is morphologically similar to cell death associated with normal vertebrate development and polyglutamine-induced neurodegeneration. Our results may therefore provide molecular inroads to understanding nonapoptotic cell death in metazoan development and disease.