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Tissue Specific Roles of Dynein Light Chain 1 in Regulating Germ Cell Apoptosis in Ceanorhabditis elegans

Research output: Book/anthology/dissertation/reportPh.D. thesisResearch

  • Tine Hørning Morthorst
Apoptosis is the process in which external or internal cues activate certain killing pathways in a cell to induce self-elimination. Apoptosis is a conserved key process required to modulate embryogenesis and for removal of damaged or superfluous cells. Dysregulation of apoptosis is implicated in the etiology of many diseases, including cancer, neurodegenerative, cardiovascular and autoimmune diseases. Several of the first genes found to regulate apoptosis were discovered in the nematode Caenorhabditis elegans.
In this project, two different and tissue specific roles of C. elegans dynein light chain 1 (dlc-1) in apoptosis are described. DLC-1 is a part of the motor complex dynein, which moves along microtubules inside the cell. DLC-1 has been demonstrated to have both dynein dependent and independent functions in mammalian cells, which is also apparent from the studies presented here. Specifically, DLC-1 was found to play a cell-nonautonomous role in somatic tissue to negatively regulate the apoptotic response to ironizing radiation-induced apoptosis upstream of the KRIT1/CCM1 homolog KRI-1. Depletion of dlc-1 results in ectopic apoptosis in the germline, which is dependent on the BH3-only proteins EGL-1 and CED-13. These proteins are normally regulated by the p53 homolog CEP-1, however, DLC-1 regulates apoptosis independently of the function of CEP-1. Furthermore, the function of DLC-1 is independent of its association with dynein.
The other apoptotic mechanism of DLC-1 regulates physiological apoptosis inside the dying germ cells through a dynein-dependent pathway. DLC-1 and dynein heavy chain (DHC-1) localizes to the nuclear membrane of apoptotic germ cells, and depletion of either one inhibits the induction of physiological apoptosis, but not damage induced apoptosis. Their pro-apoptotic function seems to be dependent on a functional engulfment machinery, as depletion of dlc-1 or dhc-1 only affects apoptosis in engulfment defective mutants.
Lastly, DLC-1 was found to affect the localization of the engulfment receptor CED-1, probably by mediating the activity of clathrin mediated endocytosis. Furthermore, the adaptor protein CED-6 was found to act as a possible CLASP for CED-1 to mediate internalization of this receptor through clathrin mediated endocytosis.
Original languageEnglish
Number of pages209
Commissioning bodyGraduate School of Science and Technology
Publication statusPublished - 24 Sep 2015

    Research areas

  • apoptosis, c. elegans, dynein

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