Abstract
The ability to eliminate undesired cells by apoptosis is a key mechanism to maintain organismal health and homeostasis. Failure to clear apoptotic cells efficiently can cause autoimmune diseases in mammals. Genetic studies in Caenorhabditis elegans have greatly helped to decipher the regulation of apoptotic cell clearance. In this study, we show that the loss of levamisole-sensitive acetylcholine receptor, but not of a typical neuronal acetylcholine receptor causes a reduction in the number of persistent cell corpses in worms suffering from an engulfment deficiency. This reduction is not caused by impaired or delayed cell death but rather by a partial restoration of the cell clearance capacity. Mutants in acetylcholine turn-over elicit a similar phenotype, implying that acetylcholine signaling is the process responsible for these observations. Surprisingly, tissue specific RNAi suggests that UNC-38, a major component of the levamisole-sensitive receptor, functions in the dying germ cell to influence engulfment efficiency. Animals with loss of acetylcholine receptor exhibit a higher fraction of cell corpses positive for the “eat-me” signal phosphatidylserine. Our results suggest that modulation by ion channels of ion flow across plasma membrane in dying cells can influence the dynamics of phosphatidylserine exposure and thus clearance efficiency.
Highlights
Efficient clearance of dead cells is key for proper organismal health and homeostasis
ACh Signaling Loss Reduces Cell Clearance Deficiencies in C. elegans we performed a series of double mutant analyses: we crossed mutations in genes coding for subunits of the muscular and various neuronal AChRs into three engulfment deficient backgrounds: ced-5, ced-6 and ced-10, representing the two classical engulfment pathways and the GTPase upon which they converge [13] and scored the number of persistent cell corpses in the L1 head
In this study we report our observation that loss of ACh signaling through the levamisolereceptor results in a reduction in the number of persistent cell corpses in worms suffering from a defect in apoptotic cell clearance
Summary
Efficient clearance of dead cells is key for proper organismal health and homeostasis. Dying cells that are not properly removed can release harmful cellular contents into the surrounding tissue, potentially resulting in inflammation and autoimmune disease [1, 2]. The nematode Caenorhabditis elegans has been used with great success as a model to study the molecular basis of apoptosis and cell clearance. Apoptotic cells in C. elegans are rapidly engulfed and digested. As there are no professional phagocytes in C. elegans, this function is performed by adjacent cells [3]. Apoptotic germ cells are engulfed by the surrounding gonadal sheath cells [4]. As is the case in mammals, dying cells in C. elegans expose
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