Programmed elimination of cells by caspase-independent cell extrusion in C. elegans
Open Access
- 15 July 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 488 (7410), 226-230
- https://doi.org/10.1038/nature11240
Abstract
Cells programmed to die during C. elegans embryogenesis can be eliminated from the embryo and undergo apoptosis in the absence of caspase activity via an extrusion mechanism that depends on activation of the AMPK-related kinase PIG-1 by an LKB1-like kinase complex. Programmed cell death is an important part of normal development, used to eliminate defective or overabundant cells and in response to infection, for instance. Most such cell deaths are a result of mechanisms dependent on a family of proteases known as caspases. Caspase-independent cell death does occur, but the mechanisms involved are not well understood. Here, Robert Horvitz and colleagues describe how cells that are programmed to die during the development of the nematode Caenorhabditis elegans can be eliminated in a caspase-independent manner. These cells are extruded from the developing embryo even in the absence of caspase activity, and appear almost identical to apoptotic cells. The authors identify an AMPK-related kinase pathway required for this form of apoptosis. 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 damage1. Although many cells are removed through caspase-mediated apoptosis followed by phagocytosis by engulfing cells2, other mechanisms of cell elimination occur3, including the extrusion of cells from epithelia through a poorly understood, possibly caspase-independent, process4. 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.This publication has 40 references indexed in Scilit:
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