RRC ID 30632
著者 Denning DP, Hatch V, Horvitz HR.
タイトル Programmed elimination of cells by caspase-independent cell extrusion in C. elegans.
ジャーナル Nature
Abstract 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 STRADα and MO25α. 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.
巻・号 488(7410)
ページ 226-30
公開日 2012-8-9
DOI 10.1038/nature11240
PII nature11240
PMID 22801495
PMC PMC3416925
MeSH Animals Apoptosis* Caenorhabditis elegans / cytology* Caenorhabditis elegans / embryology* Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism Caspases* / deficiency Caspases* / genetics Caspases* / metabolism Cell Adhesion Molecules / deficiency Cell Adhesion Molecules / metabolism Cell Shape Embryo, Nonmammalian / cytology* Embryo, Nonmammalian / embryology Embryo, Nonmammalian / enzymology* Embryonic Development Endocytosis Multiprotein Complexes / chemistry Multiprotein Complexes / metabolism Mutation Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism*
IF 42.779
引用数 46
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm1956