| RRC ID |
59353
|
| 著者 |
Harders RH, Morthorst TH, Lande AD, Hesselager MO, Mandrup OA, Bendixen E, Stensballe A, Olsen A.
|
| タイトル |
Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans.
|
| ジャーナル |
Cell Death Dis
|
| Abstract |
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.
|
| 巻・号 |
9(10)
|
| ページ |
1012
|
| 公開日 |
2018-9-27
|
| DOI |
10.1038/s41419-018-1067-y
|
| PII |
10.1038/s41419-018-1067-y
|
| PMID |
30262881
|
| PMC |
PMC6160458
|
| MeSH |
Animals
Apoptosis / physiology*
Apoptosis Regulatory Proteins
Apoptotic Protease-Activating Factor 1 / metabolism*
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / metabolism*
Calcium-Binding Proteins / metabolism*
Cytoplasmic Dyneins / metabolism
Dyneins / metabolism*
Germ Cells / metabolism
Membrane Proteins / metabolism
Phosphoproteins / metabolism
Signal Transduction / physiology
|
| IF |
5.959
|
| 引用数 |
0
|
| リソース情報 |
| 線虫 |
tm1826
tm1950 |
