Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans
| Autor: | Tine Hørning Morthorst, Emøke Bendixen, Anders Olsen, Anna Dippel Lande, Allan Stensballe, Marianne Overgaard Hesselager, Ole Aalund Mandrup, Rikke Hindsgaul Harders |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cytoplasmic Dyneins
0301 basic medicine Cancer Research Somatic cell Immunology Dynein Apoptosis Cell fate determination Article 03 medical and health sciences Cellular and Molecular Neuroscience Microtubule medicine Animals APAF1 Nuclear membrane lcsh:QH573-671 Caenorhabditis elegans Caenorhabditis elegans Proteins biology lcsh:Cytology Calcium-Binding Proteins Dyneins Membrane Proteins Cell Biology Phosphoproteins biology.organism_classification Cell biology Apoptotic Protease-Activating Factor 1 Germ Cells 030104 developmental biology medicine.anatomical_structure Apoptosis Regulatory Proteins Intracellular Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 10, Pp 1-13 (2018) Harders, R H, Morthorst, T H, Lande, A D, Hesselager, M O, Mandrup, O A, Bendixen, E, Stensballe, A & Olsen, A 2018, ' Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans ', Cell Death and Disease, vol. 9, no. 10, 1012 . https://doi.org/10.1038/s41419-018-1067-y Harders, R H, Morthorst, T H, Lande, A D, Hesselager, M O, Mandrup, O A, Bendixen, E, Stensballe, A & Olsen, A 2018, ' Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans ', Cell Death & Disease, vol. 9, no. 10, 1012 . https://doi.org/10.1038/s41419-018-1067-y Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Apoptosis ensures removal of damaged cells and helps shape organs during development by removing excessive cells. To prevent the intracellular content of the apoptotic cells causing damage to surrounding cells, apoptotic cells are quickly cleared by engulfment. Tight regulation of apoptosis and engulfment is needed to prevent several pathologies such as cancer, neurodegenerative and autoimmune diseases. There is increasing evidence that the engulfment machinery can regulate the execution of apoptosis. However, the underlying molecular mechanisms are poorly understood. We show that dynein mediates cell non-autonomous cross-talk between the engulfment and apoptotic programs in the Caenorhabditis elegans germline. Dynein is an ATP-powered microtubule-based molecular motor, built from several subunits. Dynein has many diverse functions including transport of cargo around the cell. We show that both dynein light chain 1 (DLC-1) and dynein heavy chain 1 (DHC-1) localize to the nuclear membrane inside apoptotic germ cells in C. elegans. Strikingly, lack of either DLC-1 or DHC-1 at the nuclear membrane inhibits physiological apoptosis specifically in mutants defective in engulfment. This suggests that a cell fate determining dialogue takes place between engulfing somatic sheath cells and apoptotic germ cells. The underlying mechanism involves the core apoptotic protein CED-4/Apaf1, as we find that DLC-1 and the engulfment protein CED-6/GULP are required for the localization of CED-4 to the nuclear membrane of germ cells. A better understanding of the communication between the engulfment machinery and the apoptotic program is essential for identifying novel therapeutic targets in diseases caused by inappropriate engulfment or apoptosis. |
| Databáze: | OpenAIRE |
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