Molecular and Genetic Analysis of C. elegans psr-1 in the Cell-Corpse Engulfment Process
Date Issued
2005
Date
2005
Author(s)
Hsu, Pei-Ken
DOI
en-US
Abstract
In multicellular organisms, the proper removal of apoptotic cell corpses prevents the possible dispersal of harmful cellular contents from dying cells. In C. elegans, PSR-1 is proposed to function as a receptor and act upstream of the pathway mediated by CED-2, CED-5, CED-10, and CED-12, possibly through physical interaction with CED-5 and CED-12 to control the engulfment process (Wang et al., 2003). We further mapped the binding region in PSR-1 for CED-5 and CED-12 interaction. To examine the expression pattern of PSR-1, we generated mouse and rabbit polyclonal antibodies against GST-PSR-1-IN fusion protein in order to test the subcellular localization of PSR-1. However, these antibodies and α-human PSR antibodies fail to recognize either bacterially-expressed GST-PSR-1-IN or endogenous or overexpressed PSR-1 in worm lysates. In addition to a transmembrane domain (TM), PSR-1 is predicted to possess two nuclear localization signals (NLSs). To test if any of these motifs is important for PSR-1 function, we performed deletion assays. We found that TM but not NLS is important for the engulfment function of PSR-1. These results support the previous hypothesis that PSR-1 functions on the cell membrane and possibly as a receptor to promote cell corpses uptake.
In order to investigate the relationship between psr-1 and other possible engulfment genes, mer-1, unc-73, and mig-2, we analyzed the numbers of corpse in double and triple mutants. We showed that psr-1 and another engulfment receptor, mer-1, act in the same genetic pathway, and that there is no direct interaction between PSR-1 and MER-1 intracellular or extracellular domains. Besides, unc-73 and mig-2 may play minor roles and act in the same genetic pathway which does not involve psr-1 to control cell-corpse engulfment.
Together our experiments suggested that PSR-1 may act as a membrane receptor to regulate cell-corpse engulfment and that it may function with MER-1 to achieve this process.
Subjects
線蟲
細胞屍體
吞噬
psr
cell-corpse
engulfment
Type
other
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