Publication Date:
2012-07-18
Description:
The elimination of unnecessary or defective cells from metazoans occurs during normal development and tissue homeostasis, as well as in response to infection or cellular damage. Although many cells are removed through caspase-mediated apoptosis followed by phagocytosis by engulfing cells, other mechanisms of cell elimination occur, including the extrusion of cells from epithelia through a poorly understood, possibly caspase-independent, process. Here we identify a mechanism of cell extrusion that is caspase independent and that can eliminate a subset of the Caenorhabditis elegans cells programmed to die during embryonic development. In wild-type animals, these cells die soon after their generation through caspase-mediated apoptosis. However, in mutants lacking all four C. elegans caspase genes, these cells are eliminated by being extruded from the developing embryo into the extra-embryonic space of the egg. The shed cells show apoptosis-like cytological and morphological characteristics, indicating that apoptosis can occur in the absence of caspases in C. elegans. We describe a kinase pathway required for cell extrusion involving PAR-4, STRD-1 and MOP-25.1/-25.2, the C. elegans homologues of the mammalian tumour-suppressor kinase LKB1 and its binding partners STRADalpha and MO25alpha. The AMPK-related kinase PIG-1, a possible target of the PAR-4-STRD-1-MOP-25 kinase complex, is also required for cell shedding. PIG-1 promotes shed-cell detachment by preventing the cell-surface expression of cell-adhesion molecules. Our findings reveal a mechanism for apoptotic cell elimination that is fundamentally distinct from that of canonical programmed cell death.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416925/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416925/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Denning, Daniel P -- Hatch, Victoria -- Horvitz, H Robert -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Aug 9;488(7410):226-30. doi: 10.1038/nature11240.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22801495" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Apoptosis
;
Caenorhabditis elegans/*cytology/*embryology/enzymology/genetics
;
Caenorhabditis elegans Proteins/genetics/*metabolism
;
Carrier Proteins/metabolism
;
*Caspases/deficiency/genetics/metabolism
;
Cell Adhesion Molecules/deficiency/metabolism
;
Cell Shape
;
Embryo, Nonmammalian/*cytology/embryology/*enzymology
;
Embryonic Development
;
Endocytosis
;
Multiprotein Complexes/chemistry/metabolism
;
Mutation
;
Protein-Serine-Threonine Kinases/genetics/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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